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Nijmegen, Netherlands

Radboud University Nijmegen is a public university with a strong focus on research located in Nijmegen, the Netherlands. Established since 17-10-1923 and situated in the oldest city of the Netherlands, it has seven faculties and enrolls over 19,130 students. Radboud was internationally ranked by QS World University Rankings, and placed at 136th. Wikipedia.


Lopez-Polin G.,Autonomous University of Madrid | Gomez-Navarro C.,Autonomous University of Madrid | Parente V.,CSIC - Institute of Materials Science | Guinea F.,CSIC - Institute of Materials Science | And 3 more authors.
Nature Physics | Year: 2015

The extraordinary strength, stiffness and lightness of graphene have generated great expectations of its application in flexible electronics and as a mechanical reinforcement agent. However, the presence of lattice defects, unavoidable in sheets obtained by scalable routes, might degrade its mechanical properties. Here we report a systematic study on the elastic modulus and strength of graphene with a controlled density of defects. Counter-intuitively, the in-plane Youngâ €™ s modulus increases with increasing defect density up to almost twice the initial value for a vacancy content of â 1/40.2%. For a higher density of vacancies, the elastic modulus decreases with defect inclusions. The initial increase in Youngâ €™ s modulus is explained in terms of a dependence of the elastic coefficients on the momentum of flexural modes predicted for two-dimensional membranes. In contrast, the fracture strength decreases with defect density according to standard fracture continuum models. These quantitative structure-property relationships, measured in atmospheric conditions, are of fundamental and technological relevance and provide guidance for applications in which graphene mechanics represents a disruptive improvement. © 2014 Macmillan Publishers Limited. All rights reserved.


Roelofs A.,Radboud University Nijmegen
Quarterly Journal of Experimental Psychology | Year: 2012

A few studies have examined selective attention in Stroop task performance through ex-Gaussian analyses of response time (RT) distributions. It has remained unclear whether the tail of the RT distribution in vocal responding reflects spatial integration of relevant and irrelevant attributes, as suggested by Spieler, Balota, and Faust (2000). Here, two colour-word Stroop experiments with vocal responding are reported in which the spatial relation between colour and word was manipulated. Participants named colours (e.g., green; say "green") while trying to ignore distractors that were incongruent or congruent words (e.g., red or green), or neutral series of Xs. The vocal RT was measured. Colour words in colour, white words superimposed onto colour rectangles (Experiment 1), and colour rectangles combined with auditory words (Experiment 2) yielded Stroop effects in both the leading edge and the tail of the RT distributions. These results indicate that spatial integration is not necessary for effects in the tail to occur in vocal responding. It is argued that the findings are compatible with an association of the tail effects with task conflict. © 2012 Copyright The Experimental Psychology Society.


Pruijn G.J.M.,Radboud University Nijmegen
Frontiers in Immunology | Year: 2015

The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis (RA) had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalog of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially RA. © 2015 Pruijn.


Lewis G.F.,University of Sydney | van Oirschot P.,Radboud University Nijmegen
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2012

It has recently been claimed that the Hubble sphere represents a previously unknown limit to our view of the universe, with light we detect today coming from a proper distance less than this 'cosmic horizon' at the present time. By considering the paths of light rays in several cosmologies, we show that this claim is not generally true. In particular, in cosmologies dominated by phantom energy (with an equation of state of ω < -1) the proper distance to the Hubble sphere decreases, and light rays can cross it more than once in both directions; such behaviour further diminishes the claim that the Hubble sphere is a fundamental, but unrecognized, horizon in the universe. © 2012 The Authors. Monthly Notices of the Royal Astronomical Society. © 2012 RAS.


Bernier J.,A+ Network | Poortmans P.,Radboud University Nijmegen
Breast | Year: 2015

Women harbouring BRCA1/2 mutations are known to be at higher lifetime risk of developing breast cancer than non-carriers. Compared to mastectomy, conservative surgery is also associated, in this patient population, with a higher probability to developing recurrent ipsilateral breast cancer following primary treatment. To reduce these risks, the management of BRCA1/2 - associated cancers has therefore focused on optimal prophylactic and therapeutic interventions at the time of diagnosis. In a recent past, comparative analyses of radiosensitivity levels have been carried out in murine embryos harbouring BRCA1/2 gene mutation and in non-carriers. The fact that a number of these experimental data are in favour of higher radiosensitivity levels in carriers of germline mutations leads to concern regarding the potential consequences of exposure to radiation, especially in terms of excessive toxicity in normal tissues and radiation-induced malignancies. The objective of this review is to determine whether or not the potentially higher radiosensitivity of normal and tumour cells has a clinical relevance in BRCA1/2 mutations carriers in terms of disease control, acute and late adverse events, and tumourigenesis. © 2014 Elsevier Ltd.


Janner A.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2010

The aim of this paper is to relate morphological properties of single biomacromolecules based on molecular enclosing forms indexed by an appropriate form lattice to the symmetry of the crystal where the molecules are periodically packed. Similar to the way in which the molécule intégrante of Haüy permitted a molecular interpretation of the law of rational indices of crystal growth forms, alternative molecular enclosing forms, indexed by a so-called packing lattice, allow one to bridge the gap between form and crystal lattices. In this first part, selected tutorial examples illustrate the validity of the approach and the crystallographic compatibility between molecular and crystal structures. In particular, integral molecular lattices are shown to imply the observed axial ratios between crystal lattice parameters, leading sometimes to surprising results, like a cubic crystal lattice with a unit cell having a trigonal molecular filling with hexagonal enclosing form. © 2010 International Union of Crystallography. Printed in Singapore-all rights reserved.


van Spriel A.B.,Radboud University Nijmegen | de Jong E.C.,University of Amsterdam
Journal of Leukocyte Biology | Year: 2013

Over 40 years of research into the field of DCs has revolutionized our understanding into the activation and regulation of the immune system. This minireview discusses the major breakthroughs in DC science that have paved the way to the 2011 Nobel Prize in Physiology- Medicine awarded to Bruce A. Beutler and Jules A. Hoffmann (for their discoveries in innate immune recognition) and Ralph M. Steinman (for his discovery of the DC). © Society for Leukocyte Biology.


Gemmeke J.F.,Radboud University Nijmegen | Virtanen T.,Tampere University of Technology | Hurmalainen A.,Tampere University of Technology
IEEE Transactions on Audio, Speech and Language Processing | Year: 2011

This paper proposes to use exemplar-based sparse representations for noise robust automatic speech recognition. First, we describe how speech can be modeled as a linear combination of a small number of exemplars from a large speech exemplar dictionary. The exemplars are time-frequency patches of real speech, each spanning multiple time frames. We then propose to model speech corrupted by additive noise as a linear combination of noise and speech exemplars, and we derive an algorithm for recovering this sparse linear combination of exemplars from the observed noisy speech. We describe how the framework can be used for doing hybrid exemplar-based/HMM recognition by using the exemplar-activations together with the phonetic information associated with the exemplars. As an alternative to hybrid recognition, the framework also allows us to take a source separation approach which enables exemplar-based feature enhancement as well as missing data mask estimation. We evaluate the performance of these exemplar-based methods in connected digit recognition on the AURORA-2 database. Our results show that the hybrid system performed substantially better than source separation or missing data mask estimation at lower signal-to-noise ratios (SNRs), achieving up to 57.1% accuracy at SNR=- 5 db. Although not as effective as two baseline recognizers at higher SNRs, the novel approach offers a promising direction of future research on exemplar-based ASR. © 2006 IEEE.


Straatman L.V.,Radboud University Nijmegen
The Journal of the Acoustical Society of America | Year: 2010

Cochlear implants are largely unable to encode voice pitch information, which hampers the perception of some prosodic cues, such as intonation. This study investigated whether children with a cochlear implant in one ear were better able to detect differences in intonation when a hearing aid was added in the other ear ("bimodal fitting"). Fourteen children with normal hearing and 19 children with bimodal fitting participated in two experiments. The first experiment assessed the just noticeable difference in F0, by presenting listeners with a naturally produced bisyllabic utterance with an artificially manipulated pitch accent. The second experiment assessed the ability to distinguish between questions and affirmations in Dutch words, again by using artificial manipulation of F0. For the implanted group, performance significantly improved in each experiment when the hearing aid was added. However, even with a hearing aid, the implanted group required exaggerated F0 excursions to perceive a pitch accent and to identify a question. These exaggerated excursions are close to the maximum excursions typically used by Dutch speakers. Nevertheless, the results of this study showed that compared to the implant only condition, bimodal fitting improved the perception of intonation.


Batenburg A.,VU University Amsterdam | Das E.,Radboud University Nijmegen
Journal of Medical Internet Research | Year: 2014

Background: Due to mixed findings in research on the effect of online peer-to-peer support on psychological well-being, there is a need for studies explaining why and when online support communities are beneficial for cancer patients. Objective: Previous studies have typically not taken into account individual coping differences, despite the fact that patients have different strategies to cope with cancer-related emotions. In the current study, it was predicted that the effects of online support group participation would partly depend on patients' ability to cope with thoughts and emotions regarding the illness. Methods: For this study, 184 Dutch breast cancer patients filled out a questionnaire assessing activity within a peer-led online support community, coping with emotions and thoughts regarding the illness (cognitive avoidance, emotional processing, and expression) and psychological well-being (depression, breast cancer-related concerns, and emotional well-being). Of these, 163 patients were visiting an online peer-led support community. Results: Results showed interactions of the intensity of support group participation and coping style on psychological well-being. Specifically, we found an interaction of online activity and emotional expression on depression (beta=-.17, P=.030), a marginally significant interaction of online activity and emotional expression on emotional well-being (beta=.14, P=.089), and an interaction of online activity and cognitive avoidance on breast cancer-related concerns (beta=.15, P=.027). For patients who actively dealt with their emotions and thoughts, active online support group participation was positively related to psychological well-being. For patients high on avoidance of illness-related thoughts or low on emotional expression, active participation was negatively related to measures of well-being. Conclusions: The current study revealed the role of individual differences in coping in online support group participation. Results suggest that breast cancer patients' ability to cope with emotions and thoughts regarding the illness influence the relationship between online support group participation and psychological well-being.


Krebbers R.,Radboud University Nijmegen
Conference Record of the Annual ACM Symposium on Principles of Programming Languages | Year: 2014

The C11 standard of the C programming language does not specify the execution order of expressions. Besides, to make more effective optimizations possible (eg. delaying of side-effects and interleaving), it gives compilers in certain cases the freedom to use even more behaviors than just those of all execution orders. Widely used C compilers actually exploit this freedom given by the C standard for optimizations, so it should be taken seriously in formal verification. This paper presents an operational and axiomatic semantics (based on separation logic) for non-determinism and sequence points in C. We prove soundness of our axiomatic semantics with respect to our operational semantics. This proof has been fully formalized using the Coq proof assistant. © 2014 ACM.


Veldhuijzen D.S.,University Utrecht | Sondaal S.F.V.,University Utrecht | Oosterman J.M.,Radboud University Nijmegen
Journal of Pain | Year: 2012

Patients with fibromyalgia frequently report cognitive complaints. In this study we examined performance on 2 cognitive inhibition tests, the Stroop Color-Word Test (SCWT) and the Multi-Source Interference Test (MSIT), in 35 female patients with fibromyalgia and 35 age-matched healthy female controls. Experimental pressure pain thresholds (PPT) were determined, and fibromyalgia patients rated their current pain on a visual analog scale and completed the pain and fatigue subscales of the Fibromyalgia Impact Questionnaire. Further, all subjects completed questionnaires assessing symptoms of pain catastrophizing, depression, and anxiety. Significant group differences were found for SCWT and MSIT performance in both the neutral (N) and interference (I) conditions with slower reaction times in patients versus controls. However, no significant group differences were found for the difference (I-N) or proportion (I/N) scores, or on the number of errors made. For patients, pain experienced during PPT correlated significantly to several indices of cognition. Psychosocial variables were not related to cognitive test performance. Fibromyalgia patients performed worse on both tests but to a similar extent for the neutral condition and the interference condition, indicating that there is no specific problem in cognitive inhibition. Evidence of decreased mental processing and/or psychomotor speed was found in patients with fibromyalgia. Perspective: Fibromyalgia patients performed worse on interference tests, but no specific problem in cognitive inhibition was found. Decreased reaction time performance may instead point to an underlying problem of psychomotor or mental processing speed in fibromyalgia. Future studies should examine potential deficits in psychomotor function in fibromyalgia patients in more detail. © 2012 by the American Pain Society.


Janssen T.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2012

Historians often have debates about the beginning and end of a certain era. The same discussion can be had about the history of aperiodic crystals. There are reasons to claim that in 2012 one may celebrate the 50th anniversary of this field. A short description is given of the development of this branch of crystallography. It is argued that the most important point in its history is the discovery of quasicrystals, which has been recognized by awarding the Nobel Prize in Chemistry 2011 to Dan Shechtman. © 2012 International Union of Crystallography Printed in Singapore-all rights reserved.


Doni G.,University of Applied Sciences and Arts Southern Switzerland | Doni G.,University of Lugano | Kostiainen M.A.,Radboud University Nijmegen | Danani A.,University of Applied Sciences and Arts Southern Switzerland | Pavan G.M.,University of Applied Sciences and Arts Southern Switzerland
Nano Letters | Year: 2011

In this work molecular dynamics simulation identifies a clear link between the dendron-virus multivalent molecular recognition and the nature of the consequent self-assembly. Data demonstrate how a weak hydrophobic association is transformed in an electrostatic self-assembly, orders of magnitude stronger, depending on the dendron generation used to assemble the viruses. This opens a new frontier in the engineering of hierarchical self-assemblies, potentially enabling the control of the supramolecular properties by acting at the single-molecule level. © 2010 American Chemical Society.


Ouborg N.J.,Radboud University Nijmegen | Pertoldi C.,University of Aarhus | Loeschcke V.,University of Aarhus | Bijlsma R.K.,University of Groningen | Hedrick P.W.,Arizona State University
Trends in Genetics | Year: 2010

Over the past twenty years conservation genetics has progressed from being mainly a theory-based field of population biology to a full-grown empirical discipline. Technological developments in molecular genetics have led to extensive use of neutral molecular markers such as microsatellites in conservation biology. This has allowed assessment of the impact of genetic drift on genetic variation, of the level of inbreeding within populations, and of the amount of gene flow between or within populations. Recent developments in genomic techniques, including next generation sequencing, whole genome scans and gene-expression pattern analysis, have made it possible to step up from a limited number of neutral markers to genome-wide estimates of functional genetic variation. Here, we focus on how the transition of conservation genetics to conservation genomics leads to insights into the dynamics of selectively important variation and its interaction with environmental conditions, and into the mechanisms behind this interaction. © 2010 Elsevier Ltd.


Paci E.,ISPO Cancer Prevention and Research Institute | Broeders M.,Radboud University Nijmegen | Hofvind S.,Oslo University College | Puliti D.,ISPO Cancer Prevention and Research Institute | Duffy S.W.,Queen Mary, University of London
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

A recent comprehensive review has been carried out to quantify the benefits and harms of the European population-basedmammographic screening programs. Five literature reviews were conducted on the basis of the observational published studies evaluating breast cancer mortality reduction, breast cancer overdiagnosis, and false-positive results. On the basis of the studies reviewed, the authors present a first estimate of the benefit and harm balance sheet. For every 1,000 women screened biennially from ages 50 to 51 years until ages 68 to 69 years and followed up until age 79 years, an estimated seven to nine breast cancer deaths are avoided, four cases are overdiagnosed, 170 women have at least one recall followed by noninvasive assessment with a negative result, and 30 women have at least one recall followed by invasive procedures yielding a negative result. The chance of a breast cancer death being avoided by populationbased mammography screening of appropriate quality is more than that of overdiagnosis by screening. These outcomes should be communicated to women offered service screening in Europe. © 2014 American Association for Cancer Research.


Kleiss R.,Radboud University Nijmegen | Van Den Oord G.,Nikhef
Computer Physics Communications | Year: 2011

We present a new Monte Carlo tool that computes full tree-level matrix elements in high-energy physics. The program accepts user-defined models and has no restrictions on the process multiplicity. To achieve acceptable performance, CAMORRA evaluates the matrix elements in a recursive way by combining off-shell currents. Furthermore, CAMORRA can be used to compute amplitudes involving continuous color and helicity final states. © 2010 Elsevier B.V. All rights reserved.


Brock R.,Radboud University Nijmegen
Bioconjugate Chemistry | Year: 2014

Over the past 20 years, cell-penetrating peptides (CPPs) have captured the attention of biomedical researchers, biophysicists, and (bio)organic chemists. These molecules efficiently enter cells and mediate entry of (macro)molecules that by themselves do not cross the plasma membrane. Since their discovery, models on the mechanism by which uptake occurs have seen major revisions. Starting from direct penetration across the plasma membrane, it later became apparent that for large molecular weight cargos in particular, endocytosis plays a role in uptake and furthermore that the route of uptake is a function of CPP, cell-type, cargo, and concentration. For the class of arginine-rich CPPs, this dependence on conditions has been elucidated in particular. As I will discuss here for this class of CPPs, a downside of this multitude of possibilities has been a lack of attention for commonalities in the observation of apparently distinct phenomena. At the same time, differences of apparently similar observations were not appreciated sufficiently. In addition, there has been insufficient acknowledgment of observations that are incompatible with the proposed models. Nevertheless, a considerable amount of data can be assembled into a quite coherent picture and the data that is left creates the basis for concrete future lines of research to resolve the questions that remain. Moreover, any uptake mechanism has its distinct structure-activity relationship for uptake giving room for the molecular design of molecules to preferentially direct uptake to either of them. © 2014 American Chemical Society.


De Coninck H.,Radboud University Nijmegen | Benson S.M.,Stanford University
Annual Review of Environment and Resources | Year: 2014

Almost 20 years ago, the first CO2 capture and storage (CCS) project began injecting CO2 into a deep geological formation in an offshore aquifer. Relevant science has advanced in areas such as chemical engineering, geophysics, and social psychology. Governments have generously funded demonstrations. As a result, a handful of industrial-scale CCS projects are currently injecting about 15 megatons of CO2 underground annually that contribute to climate changemitigation.However, CCS is struggling to gain a foothold in the set of options for dealing with climate change. This review explores why and discusses critical conditions for CCS to emerge as a viable mitigation option. Explanations for this struggle include the absence of government action on climate change, economic crisis-induced low carbon prices, public skepticism, increasing costs, and advances in other options including renewables and shale gas. Climate change action is identified as a critical condition for progress in CCS, in addition to community support, safe storage, robust policy support, and favorable CCS market conditions. Copyright © 2014 by Annual Reviews. All rights reserved.


Boukhvalov D.W.,Korea Institute for Advanced Study | Katsnelson M.I.,Radboud University Nijmegen | Son Y.-W.,Korea Institute for Advanced Study
Nano Letters | Year: 2013

Water inside the low-dimensional carbon structures has been considered seriously owing to fundamental interest in its flow and structures as well as its practical impact. Recently, the anomalous perfect penetration of water through graphene oxide membrane was demonstrated although the membrane was impenetrable for other liquids and even gases. The unusual auxetic behavior of graphene oxide in the presence of water was also reported. Here, on the basis of first-principles calculations, we establish atomistic models for hybrid systems composed of water and graphene oxides revealing the anomalous water behavior inside the stacked graphene oxides. We show that formation of hexagonal ice bilayer in between the flakes as well as melting transition of ice at the edges of flakes are crucial to realize the perfect water permeation across the whole stacked structures. The distance between adjacent layers that can be controlled either by oxygen reduction process or pressure is shown to determine the water flow thus highlighting a unique water dynamics in randomly connected two-dimensional spaces. © 2013 American Chemical Society.


Koch B.,University of Santiago de Chile | Saueressig F.,Radboud University Nijmegen
Classical and Quantum Gravity | Year: 2014

We study the quantum modifications of classical, spherically symmetric Schwarzschild (anti-) de Sitter black holes within quantum Einstein gravity. The quantum effects are incorporated through the running coupling constants Gk and Λk, computed within the exact renormalization group approach, and a common scale-setting procedure. We find that, in contrast to common intuition, it is actually the cosmological constant that determines the short-distance structure of the RG-improved black hole: in the asymptotic UV the structure of the quantum solutions is universal and given by the classical Schwarzschild-de Sitter solution, entailing a self-similarity between the classical and quantum regime. As a consequence asymptotically safe black holes evaporate completely and no Planck-size remnants are formed. Moreover, the thermodynamic entropy of the critical Nariai black hole is shown to agree with the microstate count based on the effective average action, suggesting that the entropy originates from quantum fluctuations around the mean-field geometry. © 2014 IOP Publishing Ltd.


Aims: To test whether (i) drinking motives predict the frequency of pre-drinking (i.e. alcohol consumption before going out); (ii) drinking motives predict HDGE (heavy drinking on a given evening: 4+ for women, 5+ for men) and related adverse consequences (hangover, injuries, blackouts, etc.), even when pre-drinking is accounted for, and (iii) drinking motives moderate the impact of pre-drinking on HDGE and consequences. Design: Using the internet-based cellphone-optimized assessment technique (ICAT), participants completed a series of cellphone questionnaires every Thursday, Friday and Saturday evening over 5 weeks. Setting: French-speaking Switzerland. Participants: A total of 183 young adults [53% female, mean age (standard deviation)=23.1 (3.1)] who completed 7828 questionnaires on 1441 evenings. Measurements: Drinking motives assessed at baseline, alcohol consumption assessed at 8 p.m., 9 p.m., 10 p.m., 11 p.m. and midnight and consequences assessed at 11 a.m. the next day. Findings: Gender-separate multi-level models revealed that pre-drinking predicted HDGE (men: B=2.17, P<0.001; women: B=2.12, P<0.001) and alcohol-related consequences (men: B=0.24, P<0.01; women: B=0.29, P<0.001). Enhancement motives were found to predict HDGE (B=0.48, P<0.05) and related consequences (B=0.09, P<0.05) among men, while among women coping motives had the same effect (HDGE: B=0.73, P<0.001; consequences: B=0.13, P<0.01). With the exception of conformity motives among women (B=0.54, P<0.05), however, no drinking motive dimension predicted the frequency of pre-drinking, while coping and conformity motives moderated the impact of pre-drinking on HDGE (men, conformity: B=-1.57, P<0.05) and its consequences (men, coping: B=-0.46, P<0.01; women, coping: B=0.76, P<0.05). Conclusions: Among young adults in Switzerland, heavy weekend drinking and the related consequences seem to result from the combination of pre-drinking, level of negative reinforcement drinking for women and positive reinforcement drinking for men. © 2013 Society for the Study of Addiction.


Yildirim B.O.,De Kluyskamp | Derksen J.J.L.,Radboud University Nijmegen
Psychiatry Research | Year: 2012

Life-course persistent antisocial behavior is 10 to 14 times more prevalent in males and it has been suggested that testosterone levels could account for this gender bias. Preliminary studies with measures of fetal testosterone find inconsistent associations with antisocial behavior, especially studies that use the 2D:4D ratio as a proxy for fetal testosterone. However, circulating testosterone consistently shows positive associations with antisocial behaviors throughout childhood, adolescence, and adulthood, particularly in males. It is suggested that high fetal/circulating testosterone interactively influence the maturation and functionality of mesolimbic dopaminergic circuitry, right orbitofrontal cortex, and cortico-subcortical connectivity, resulting in a strong reward motivation, low social sensitivity, and dampened regulation of strong motivational/emotional processes. The link between these testosterone induced endophenotypes and actual display of antisocial behavior is strongly modulated by different social (e.g., social rejection, low SES) and genetic (e.g., MAOA, 5HTT) risk factors that can disturb socio-, psycho-, and biological development and interact with testosterone in shaping behavior. When these additional risk factors are present, the testosterone induced endophenotypes may increase the risk for a chronic antisocial lifestyle. However, behavioral endophenotypes induced by testosterone can also predispose towards socially adaptive traits such as a strong achievement motivation, leadership, fair bargaining behaviors, and social assertiveness. These adaptive traits are more likely to emerge when the high testosterone individual has positive social experiences that promote prosocial behaviors such as strong and secure attachments with his caregivers, affiliation with prosocial peers, and sufficient socioeconomic resources. A theoretical model is presented, various hypotheses are examined, and future venues for research are discussed. © 2012 Elsevier Ireland Ltd.


Smit J.,Radboud University Nijmegen
Thyroid Research | Year: 2013

Therapy decisions in advanced medullary thyroid carcinoma should be guided by a critical appraisal of the natural disease course (slowly progressive vs. aggressive) and benefits and side effects of therapy. Therapy goals should be distinguished between curative and palliative. Local treatments are mainly palliative and may add to quality of life. The advent of novel systemic therapies opens promising perspectives but its place in the therapeutic arsenal must be further determined. © 2013 Smit; licensee BioMed Central Ltd.


Ulybyshev M.V.,Moscow State University | Buividovich P.V.,University of Regensburg | Katsnelson M.I.,Radboud University Nijmegen | Polikarpov M.I.,Moscow Institute of Physics and Technology
Physical Review Letters | Year: 2013

We report on the results of the first-principles numerical study of spontaneous breaking of chiral (sublattice) symmetry in suspended monolayer graphene due to electrostatic interaction, which takes into account the screening of Coulomb potential by electrons on σ orbitals. In contrast to the results of previous numerical simulations with unscreened potential, we find that suspended graphene is in the conducting phase with unbroken chiral symmetry. This finding is in agreement with recent experimental results by the Manchester group [D. C. Elias et al., Nat. Phys. 7, 701 (2011); A. S. Mayorov et al., Nano Lett. 12, 4629 (2012)]. Further, by artificially increasing the interaction strength, we demonstrate that suspended graphene is quite close to the phase transition associated with spontaneous chiral symmetry breaking, which suggests that fluctuations of chirality and nonperturbative effects might still be quite important. © 2013 American Physical Society.


Van Geijlswijk I.M.,University Utrecht | Korzilius H.P.L.M.,Radboud University Nijmegen | Smits M.G.,Hospital Gelderse Vallei
Sleep | Year: 2010

Study Objectives: To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder. Design: Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990-2009). Patients: Individuals with delayed sleep phase disorder. Interventions: Administration of melatonin. Measurements and Results: A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83 -41.72 min). The wake-up time and total sleep time did not change significantly. Conclusions: Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder.


Clark A.R.,Institute of Structural and Molecular Biology | Lubsen N.H.,Radboud University Nijmegen | Slingsby C.,Institute of Structural and Molecular Biology
International Journal of Biochemistry and Cell Biology | Year: 2012

α-Crystallin, a major component of the eye lens cytoplasm, is a large multimer formed from two members of the small heat shock protein (sHsp) family. Inherited crystallin mutations are a common cause of childhood cataract, whereas miscellaneous changes to the long-lived crystallins cause age-related cataract, the most common cause of blindness worldwide. Newly formed eye lens cells use proteostasis to deal with the consequences of mutations, whereas mature lens cells, devoid of the ATP-driven folding and degradation machines, are hypothesized to have the α-crystallin "holdase" chaperone function to prevent protein aggregation. We discuss the impact of truncating and missense mutations on α-crystallin, based on recent progress towards determining sHsp 3D structure. Dominant missense mutations to the "α-crystallin domain" of αA- (HSPB4) or αB-crystallin (HSPB5) occur on residues predicted to facilitate domain dynamics. αB-Crystallin is also expressed in striated muscle and mutations cause myopathy. The impact on these cellular cytoplasms is compared where sHsp multimer partners and metabolic constraints are different. Selected inherited mutations of the lens β- and γ-crystallins are considered in the context of their possible dependence on the "holdase" chaperone function of α-crystallin. Looking at discrete changes to specific crystallin polypeptide chains that can function as chaperone or substrate provide insights into the workings of a cytoplasmic proteostatic system. These observations provide a framework for validating the function of α-crystallin as a chaperone, or as a lens space filler adapted from a chaperone function. Understanding the mechanistic role of α-crystallins will aid progress in research into age-related cataract and adult-onset myopathy. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology.


Watt F.M.,Kings College London | Huck W.T.S.,Radboud University Nijmegen
Nature Reviews Molecular Cell Biology | Year: 2013

The field of stem cells and regenerative medicine offers considerable promise as a means of delivering new treatments for a wide range of diseases. In order to maximize the effectiveness of cell-based therapies-whether stimulating expansion of endogenous cells or transplanting cells into patients-it is essential to understand the environmental (niche) signals that regulate stem cell behaviour. One of those signals is from the extracellular matrix (ECM). New technologies have offered insights into how stem cells sense signals from the ECM and how they respond to these signals at the molecular level, which ultimately regulate their fate. © 2013 Macmillan Publishers Limited. All rights reserved.


Rovelli C.,Aix - Marseille University | Rovelli C.,University of Toulon | Vidotto F.,Radboud University Nijmegen
Physical Review Letters | Year: 2013

A simple argument indicates that covariant loop gravity (spin foam theory) predicts a maximal acceleration and hence forbids the development of curvature singularities. This supports the results obtained for cosmology and black holes using canonical methods. © 2013 American Physical Society.


Maoz D.,Tel Aviv University | Mannucci F.,National institute for astrophysics | Nelemans G.,Radboud University Nijmegen | Nelemans G.,Catholic University of Leuven
Annual Review of Astronomy and Astrophysics | Year: 2014

Type Ia supernovae (SNe Ia) are important distance indicators, element factories, cosmic-ray accelerators, kinetic-energy sources in galaxy evolution, and end points of stellar binary evolution. It has long been clear that a SN Ia must be the runaway thermonuclear explosion of a degenerate carbon-oxygen stellar core, most likely a white dwarf (WD). However, the specific progenitor systems of SNe Ia, and the processes that lead to their ignition, have not been identified. Two broad classes of progenitor binary systems have long been considered: single-degenerate (SD), in which a WD gains mass from a nondegenerate star; and double-degenerate (DD), involving the merger of two WDs. New theoretical work has enriched these possibilities with some interesting updates and variants. We review the significant recent observational progress in addressing the progenitor problem. We consider clues that have emerged from the observed properties of the various proposed progenitor populations, from studies of SN Ia sites pre- and postexplosion from analysis of the explosions themselves and from the measurement of event rates. The recent nearby and well-studied event, SN 2011fe, has been particularly revealing. The observational results are not yet conclusive and sometimes prone to competing theoretical interpretations. Nevertheless, it appears that DD progenitors, long considered the underdog option, could be behind some, if not all, SNe Ia. We point to some directions that may lead to future progress. Copyright © 2014 by Annual Reviews.


Cho K.,Radboud University Nijmegen
Electronic Proceedings in Theoretical Computer Science, EPTCS | Year: 2014

This paper presents a novel semantics for a quantum programming language by operator algebras, which are known to give a formulation for quantum theory that is alternative to the one by Hilbert spaces. We show that the opposite category of the category of W∗-algebras and normal completely positive subunital maps is an elementary quantum flow chart category in the sense of Selinger. As a consequence, it gives a denotational semantics for Selinger's first-order functional quantum programming language QPL. The use of operator algebras allows us to accommodate infinite structures and to handle classical and quantum computations in a unified way. © K. Cho.


Karlebach G.,Max Planck Institute for Psycholinguistics | Francks C.,Max Planck Institute for Psycholinguistics | Francks C.,Radboud University Nijmegen
Cortex | Year: 2015

Lateralization is an important aspect of the functional brain architecture for language and other cognitive faculties. The molecular genetic basis of human brain lateralization is unknown, and recent studies have suggested that gene expression in the cerebral cortex is bilaterally symmetrical. Here we have re-analyzed two transcriptomic datasets derived from post mortem human cerebral cortex, with a specific focus on superior temporal and auditory language cortex in adults. We applied an empirical Bayes approach to model differential left-right expression, together with gene ontology (GO) analysis and meta-analysis. There was robust and reproducible lateralization of individual genes and GO groups that are likely to fine-tune the electrophysiological and neurotransmission properties of cortical circuits, most notably synaptic transmission, nervous system development and glutamate receptor activity. Our findings anchor the cerebral biology of language to the molecular genetic level. Future research in model systems may determine how these molecular signatures of neurophysiological lateralization effect fine-tuning of cerebral cortical function, differently in the two hemispheres. © 2015 Elsevier Ltd.


Roelofs A.,Radboud University Nijmegen
Journal of Experimental Psychology: Learning Memory and Cognition | Year: 2014

Investigators have found no agreement on the functional locus of Stroop interference in vocal naming. Whereas it has long been assumed that the interference arises during spoken word planning, more recently some investigators have revived an account from the 1960s and 1970s holding that the interference occurs in an articulatory buffer after word planning. Here, 2 color-word Stroop experiments are reported that tested between these accounts using eye tracking. Previous research has indicated that the shifting of eye gaze from a stimulus to another occurs before the articulatory buffer is reached in spoken word planning. In the present experiments, participants were presented with color-word Stroop stimuli and left- or right-pointing arrows on different sides of a computer screen. They named the color attribute and shifted their gaze to the arrow to manually indicate its direction. If Stroop interference arises in the articulatory buffer, the interference should be present in the color-naming latencies but not in the gaze shift and manual response latencies. Contrary to these predictions, Stroop interference was present in all 3 behavioral measures. These results indicate that Stroop interference arises during spoken word planning rather than in articulatory buffering. © 2014 American Psychological Association.


van de Kerkhof P.C.M.,Radboud University Nijmegen
Dermatologic Clinics | Year: 2015

Topical therapies are the mainstream treatment of psoriasis because most patients have mild disease. First-line treatments are vitamin D derivatives and corticosteroids. These treatments are usually given in combination schedules. For topical treatments the selection of the most appropriate vehicle is of major importance, thus improving adherence to the treatment, which frequently is impaired by the complexities of topical therapeutic choices. Evidence for efficacy and safety of topical treatments is readily available for vitamin D treatments and short-term treatment with corticosteroids. However, the scientific evidence for longer-term treatments is limited. Multiple new small molecules are in various stages of development and are reviewed. © 2015 Elsevier Inc.


Degens H.,Manchester Metropolitan University | Gayan-Ramirez G.,Catholic University of Leuven | Van Hees H.W.H.,Radboud University Nijmegen
American Journal of Respiratory and Critical Care Medicine | Year: 2015

Smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from skeletal muscle dysfunction, and it has been suggested that cigarette smoke exposure contributes to the development of skeletal muscle dysfunction even before overt pulmonary pathology. This review summarizes the evidence that muscles of nonsymptomatic smokers are weaker and less fatigue resistant than those of nonsmokers. Although physical inactivity of many smokers contributes to some alterations observed in skeletal muscle, exposure to cigarette smoke per se can also induce skeletal muscle dysfunction. Cigarette smoke constituents and systemic inflammatory mediators enhance proteolysis and inhibit protein synthesis, leading to loss of muscle mass. Reduced skeletal muscle contractile endurance in smokers may result from impaired oxygen delivery to the mitochondria and ability of the mitochondria to generate ATP due to interaction of carbon monoxide with hemoglobin, myoglobin, and components of the respiratory chain. Besides hampering contractile function, smoking may have immediate beneficial effects on motor skills, which are attributable to nicotine. In contrast to pulmonary pathology, many of the effects of smoking on skeletal muscle are most likely reversible by smoking cessation. Copyright © 2015 by the American Thoracic Society.


Schuler M.,University of Bremen | Rosner M.,University of Bremen | Wehling T.O.,University of Bremen | Lichtenstein A.I.,University of Hamburg | Katsnelson M.I.,Radboud University Nijmegen
Physical Review Letters | Year: 2013

To understand how nonlocal Coulomb interactions affect the phase diagram of correlated electron materials, we report on a method to approximate a correlated lattice model with nonlocal interactions by an effective Hubbard model with on-site interactions U* only. The effective model is defined by the Peierls-Feynman-Bogoliubov variational principle. We find that the local part of the interaction U is reduced according to U *=U-V̄, where V̄ is a weighted average of nonlocal interactions. For graphene, silicene, and benzene we show that the nonlocal Coulomb interaction can decrease the effective local interaction by more than a factor of 2 in a wide doping range. © 2013 American Physical Society.


Pinxten W.,Hasselt University | Howard H.C.,Radboud University Nijmegen | Howard H.C.,Uppsala University
Best Practice and Research: Clinical Gastroenterology | Year: 2014

While there is ongoing discussion about the details of implementation of whole genome sequencing (WGS) and whole exome sequencing (WES), there appears to be a consensus amongst geneticists that the widespread use of these approaches is not only inevitable, but will also be beneficial [1]. However, at the present time, we are unable to anticipate the full range of uses, consequences and impact of implementing WGS and WES. Nevertheless, the already known ethical issues, both in research and in clinical practice are diverse and complex and should be addressed properly presently. Herein, we discuss the ethical aspects of WGS and WES by particularly focussing on three overlapping themes: (1) informed consent, (2) data handling, and (3) the return of results. © 2014 Elsevier Ltd. All rights reserved.


Charleux B.,CNRS Laboratory of Chemistry, Catalysis, Polymers and Process | D'Agosto F.,CNRS Laboratory of Chemistry, Catalysis, Polymers and Process | Delaittre G.,Radboud University Nijmegen
Advances in Polymer Science | Year: 2010

The synthesis of hybrid and core-shell nanoparticles using controlled/ living radical polymerization in aqueous dispersed systems is reviewed. The processes involve emulsion, miniemulsion, and dispersion polymerizations as well as grafting techniques, with the aim of producing submicrometric latex particles with well-defined morphologies that might not be accessible via classical radical polymerization. Those morphologies include organic/inorganic hybrids, nanostructured particles, (nano)capsules, and particles with a hydrophobic core and hydrophilic shell. © 2010 Springer-Verlag Berlin Heidelberg.


Rodenburg R.J.,Radboud University Nijmegen
Biochimica et Biophysica Acta - Bioenergetics | Year: 2016

Complex I deficiency is the most frequently encountered single mitochondrial single enzyme deficiency in patients with a mitochondrial disorder. Although specific genotype-phenotype correlations are very difficult to identify, the majority of patients present with symptoms caused by leukodystrophy. The poor genotype-phenotype correlations can make establishing a diagnosis a challenge. The classical way to establish a complex I deficiency in patients is by performing spectrophotometric measurements of the enzyme in a muscle biopsy or other patient-derived material (liver or heart biopsy, cultured skin fibroblasts). Complex I is encoded by both the mtDNA and nuclear DNA and pathogenic mutations have been identified in the majority of the 44 genes encoding the structural subunits of complex I. In recent years, the increasing possibilities for diagnostic molecular genetic tests of large gene panels, exomes, and even entire genomes has led to the identification of many novel genetic defects causing complex I deficiency. Complex I mutations not only result in a reduced enzyme activity but also induce secondary effects at the cellular level, such as elevated reactive oxygen species production, altered membrane potential and mitochondrial morphology. At this moment there is no cure for complex I deficiency and the treatment options for complex I patients are restricted to symptomatic treatment. Recent developments, amongst others based on the treatment of the secondary effects of complex I deficiency, have shown to be promising as new therapeutic strategies in vitro and have entered clinical trials. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt. © 2016.


Dinarello C.A.,Aurora University | Dinarello C.A.,Radboud University Nijmegen
Blood | Year: 2011

More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Tolllike receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.


Dinarello C.A.,University of Colorado at Denver | Dinarello C.A.,Radboud University Nijmegen | Fossati G.,Italfarmaco S.p.A. | Mascagni P.,Italfarmaco S.p.A.
Molecular Medicine | Year: 2011

This issue of Molecular Medicine contains 14 original research reports and state-of-the-art reviews on histone deacetylase inhibitors (HDACi's), which are being studied in models of a broad range of diseases not related to the proapoptotic properties used to treat cancer. The spectrum of these diseases responsive to HDACi's is for the most part due to several antiinflammatory properties, often observed in vitro but importantly also in animal models. One unifying property is a reduction in cytokine production as well as inhibition of cytokine postreceptor signaling. Distinct from their use in cancer, the reduction in inflammation by HDACi's is consistently observed at low concentrations compared with the higher concentrations required for killing tumor cells. This characteristic makes HDACi's attractive candidates for treating chronic diseases, since low doses are well tolerated. For example, low oral doses of the HDACi givinostat have been used in children to reduce arthritis and are well tolerated. In addition to the antiinflammatory properties, HDACi's have shown promise in models of neurodegenerative disorders, and HDACi's also hold promise to drive HIV-1 out of latently infected cells. No one molecular mechanism accounts for the non-cancer-related properties of HDACi's, since there are 18 genes coding for histone deacetylases. Rather, there are mechanisms unique for the pathological process of specific cell types. In this overview, we summarize the preclinical data on HDACi's for therapy in a wide spectrum of diseases unrelated to the treatment of cancer. The data suggest the use of HDACi's in treating autoimmune as well as chronic inflammatory diseases. © 2011 The Feinstein Institute for Medical Research.


Low T.,IBM | Low T.,Purdue University | Guinea F.,CSIC - Institute of Materials Science | Katsnelson M.I.,Radboud University Nijmegen
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

We show that when the pseudomagnetic fields created by long-wavelength deformations are appropriately coupled with a scalar electric potential, a significant energy gap can emerge due to the formation of a Haldane state. Ramifications of this physical effect are examined through the study of various strain geometries commonly seen in experiments, such as strain superlattices and wrinkled suspended graphene. Of particular technological importance, we consider setups where this gap can be tunable through electrostatic gates, allowing for the design of electronic devices not realizable with other materials. © 2011 American Physical Society.


Eijsvogels T.M.H.,Liverpool John Moores University | Eijsvogels T.M.H.,Radboud University Nijmegen | Molossi S.,Baylor College of Medicine | Lee D.-C.,Iowa State University | And 2 more authors.
Journal of the American College of Cardiology | Year: 2016

Habitual physical activity and regular exercise training improve cardiovascular health and longevity. A physically active lifestyle is, therefore, a key aspect of primary and secondary prevention strategies. An appropriate volume and intensity are essential to maximally benefit from exercise interventions. This document summarizes available evidence on the relationship between the exercise volume and risk reductions in cardiovascular morbidity and mortality. Furthermore, the risks and benefits of moderate- versus high-intensity exercise interventions are compared. Findings are presented for the general population and cardiac patients eligible for cardiac rehabilitation. Finally, the controversy of excessive volumes of exercise in the athletic population is discussed. © 2016 American College of Cardiology Foundation.


Todorov A.,Princeton University | Olivola C.Y.,Carnegie Mellon University | Dotsch R.,Radboud University Nijmegen | Mende-Siedlecki P.,Princeton University
Annual Review of Psychology | Year: 2015

Since the early twentieth century, psychologists have known that there is consensus in attributing social and personality characteristics from facial appearance. Recent studies have shown that surprisingly little time and effort are needed to arrive at this consensus. Here we review recent research on social attributions from faces. Section I outlines data-driven methods capable of identifying the perceptual basis of consensus in social attributions from faces (e.g., What makes a face look threatening?). Section II describes nonperceptual determinants of social attributions (e.g., person knowledge and incidental associations). Section III discusses evidence that attributions from faces predict important social outcomes in diverse domains (e.g., investment decisions and leader selection). In Section IV, we argue that the diagnostic validity of these attributions has been greatly overstated in the literature. In the final section, we offer an account of the functional significance of these attributions. © 2015 by Annual Reviews. All rights reserved.


Huuskonen A.,Finnish Meteorological Institute | Saltikoff E.,Finnish Meteorological Institute | Holleman I.,Radboud University Nijmegen
Bulletin of the American Meteorological Society | Year: 2014

The operational weather radar network in Europe covers more than 30 countries and contains more than 200 weather radars. The radar network is heterogeneous in hardware, signal processing, transmit/receive frequency, and scanning strategy, thus making it fundamentally different than the Next Generation Weather Radar (NEXRAD) network. Within the European National Meteorological Services (EUMETNET), a grouping of services, the Operational Program for Exchange of Weather Radar Information (OPERA) has been working since 1999 on improving the harmonization of radars and their measurements. In addition, OPERA has facilitated and stimulated the exchange of radar data between its members, among others, by the development of a radar data information model and jointly agreed data formats. Since 2011, a radar data center has been in operation, producing network-wide radar mosaics from volumetric data. An essential part of the OPERA work is the documentation of the members' best practices in radar operation and data production and the making of joint recommendations.


Cook J.L.,Radboud University Nijmegen | Cook J.L.,City University London
Neuroscience and Biobehavioral Reviews | Year: 2014

Contrary to the prevailing view, Nicolle and colleagues (2012) recently demonstrated that dorsal and ventral regions of the medial prefrontal cortex (mPFC) and temporoparietal cortex (TPC) do not distinguish between action values relating to the self and to another individual; rather, these regions differentiate whether an action is currently relevant or irrelevant to the task at hand. This finding suggests solutions to paradoxes in social cognition. The first paradox concerns self/other control: With some experimental tasks TPC activity is associated with the promotion of self over other representations; in different tasks the association is with other over self (Santiesteban et al., 2012a). The second paradox concerns the control of imitation: MPFC has been associated with both the facilitation and inhibition of imitation. Considering task-relevance (i.e. whether the participant's task is to respond according to their own action values or to respond as if they were another individual) suggests possible solutions to these paradoxes. © 2014 Elsevier Ltd.


Garzelli M.V.,University of Granada | Malamos I.,Radboud University Nijmegen
European Physical Journal C | Year: 2011

The analytical package written in FORM presented in this paper allows the computation of the complete set of Feynman Rules producing the Rational terms of kind R2 contributing to the virtual part of NLO corrections in the Standard Model of the Electroweak interactions. Building block topologies filled by means of generic scalars, vectors and fermions, allowing to build these Feynman Rules in terms of specific elementary particles, are explicitly given in the Rξ gauge class, together with the automatic dressing procedure to obtain the Feynman Rules from them. The results in more specific gauges, like the ’t Hooft Feynman one, follow as particular cases, in both the HV and the FDH dimensional regularization schemes. As a check on our formulas, the gauge independence of the total Rational contribution (R1+R2) to renormalized S-matrix elements is verified by considering the specific example of the H → γγ decay process at 1-loop. This package can be of interest for people aiming at a better understanding of the nature of the Rational terms. It is organized in a modular way, allowing a further use of some its files even in different contexts. Furthermore, it can be considered as a first seed in the effort towards a complete automation of the process of the analytical calculation of the R2 effective vertices, given the Lagrangian of a generic gauge theory of particle interactions. © 2011, The Author(s).


Carlsson J.M.,Accelrys | Carlsson J.M.,Fritz Haber Institute | Ghiringhelli L.M.,Fritz Haber Institute | Fasolino A.,Radboud University Nijmegen
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

Several experiments have revealed the presence of grain boundaries in graphene that may change its electronic and elastic properties. Here, we present a general theory for the structure of [0001] tilt grain boundaries in graphene based on the coincidence site lattice (CSL) theory. We show that the CSL theory uniquely classifies the grain boundaries in terms of the misorientation angle θ and periodicity d using two grain-boundary indices (m,n), similar to the nanotube indices. The structure and formation energy of a large set of grain boundaries generated by the CSL theory for 0<θ<60 (up to 15 608 atoms) were optimized by a hierarchical methodology and validated by density functional calculations. We find that low-energy grain boundaries in graphene can be identified as dislocation arrays. The dislocations form hillocks like those observed by scanning tunneling microscopy in graphene grown on Ir(111) for small θ that flatten out at larger misorientation angles. We find that, in contrast to three-dimensional materials, the strain created by the grain boundary can be released via out-of-plane distortions that lead to an effective attractive interaction between dislocation cores. Therefore, the dependence on θ of the formation energy parallels that of the out-of-plane distortions, with a secondary minimum at θ=32.2 where the grain boundary is made of a flat zigzag array of only 5 and 7 rings. For θ>32.2, other nonhexagonal rings are also possible. We discuss the importance of these findings for the interpretation of recent experimental results. © 2011 American Physical Society.


Sniderman A.D.,McGill University | Williams K.,University of Texas Health Science Center at San Antonio | Monroe H.M.,Our Lady of the Lake University | McQueen M.J.,McMaster University | And 2 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2011

Background: Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversialMethods and Results: This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular eventsTwelve independent reports, including 233 455 subjects and 22 950 events, were analyzedAll published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects modelWhether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44)The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C (P<0.001) and 12.0%-LDL-C (P<0.0001) and that non-HDL-C RRR was 5.0%>LDL-C (P<0.017)Only HDL-C accounted for any substantial portion of the variance of the results among the studiesWe calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markersOver a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategyConclusions: These results further validate the value of apoB in clinical care. © 2011 American Heart Association, Inc.


van der Kraan P.M.,Radboud University Nijmegen
Bio-medical materials and engineering | Year: 2014

BACKGROUND: Age is the most important risk factor for primary osteoarthritis (OA). Members of the TGF-β superfamily play a crucial role in chondrocyte differentiation and maintenance of healthy articular cartilage.OBJECTIVE: We have investigated whether age-related changes in TGF-β superfamily signaling components play a role in the relationship between OA-related cartilage degradation and aging.MATERIAL AND METHODS: The relationship between age, OA and TGF-β superfamily signaling was studied using murine experimental OA models, aging mice, bovine articular cartilage and human OA cartilage. The effects of TGF-β on cartilage homeostasis was studied with immunohistochemistry, Q-RT-PCR and signaling pathway analysis with Western blotting and the application of specific TGF-β inhibitors.RESULTS: We have found that TGF-β loses its protective effects in old cartilage. Moreover, we found that on chondrocytes, TGF-β not only signals via the canonical type I receptor ALK5 (TGFBR1) but also via the ALK1 (ACVRL1) receptor. Remarkably, signaling via ALK5 (Smad2/3 route) results in protective while ALK1 signaling (Smad1/5/8 route) results in deleterious responses in articular chondrocytes. In cartilage of aging mice it was detected that the ALK1/ALK5 ratio is significantly increased, favoring TGF-β signaling via the Smad1/5/8 route, inducing changes in chondrocyte differentiation and matrix metalloproteinase-13 (MMP-13) expression. Moreover, human OA cartilage showed a significant correlation between ALK1 and MMP-13 expression. Since in mice aging and OA in often goes hand in hand, we also analyzed age-related expression of TGF-β superfamily related signaling molecules in healthy bovine cartilage in an age range from 6 months to 14 years. In this cohort of aging cartilage, we found that mainly signaling receptors determining the Smad2/3 pathway were decreased with age while Smad1/5/8-related signaling molecules did not alter, confirming our findings in aging mice.CONCLUSIONS: Old cartilage appears to be less protected by TGF-β and shows significant alterations in TGF-β signaling pathways. Loss of the protective Smad2/3 pathway during aging can provide an explanation for the relationship between OA and aging.


Batenburg A.,VU University Amsterdam | Das E.,Radboud University Nijmegen
Journal of Medical Internet Research | Year: 2014

Background: Previous research on the effects of online peer support on psychological well-being of patients with cancer showed mixed findings. There is a need for longitudinal studies explaining if and when online peer-led support groups are beneficial. How patients cope with emotions that come along with the cancer diagnosis might influence effectiveness of online participation. Emotional approach coping is a construct encompassing the intentional use of emotional processing and emotional expression in efforts to manage adverse circumstances. Objective: In this longitudinal study, we hypothesize that mixed findings in previous research are partly caused by individual differences in coping with emotions, which may moderate the effects of online support group participation on patients' well-being. Methods: A total of 133 Dutch patients with breast cancer filled out a baseline (T0) and a follow-up (T1, 6 months later) questionnaire assessing intensity of online participation within the online support community, emotional approach coping (ie, actively processing and expressing emotions), and psychological well-being (depression, emotional well-being, and breast cancer-related concerns). There were 109 patients who visited an online support community at both points in time. Repeated measures ANOVAs assessed change in well-being over time. Results: Results showed 3-way interactions of time, online intensity of participation, and emotional approach coping on emotional well-being (F1,89=4.232, P=.04, η2 ρ=.045) and depression (F1,88=8.167, P=.005, η2 ρ=.085). Online support group participation increased emotional well-being over time for patients who scored low on emotional approach coping at T0, provided that they were highly active online. Patients who were highly active online with a high score on emotional approach coping reported no change in sense of well-being, but showed the highest score on well-being overall. Participating less frequently online was only beneficial for patients who scored high on emotional approach coping, showing an increase in well-being over time. Patients participating less frequently and with a low score on emotional approach coping reported no significant change in well-being over time. Conclusions: This study extends previous findings on the effects of online peer support in two ways: by testing changes in well-being as a function of intensity of online support group participation and by examining the role of individual differences in emotional coping styles. Findings showed no negative effects of intense support group participation. Participating frequently online was especially helpful for patients who approach their emotions less actively; their emotional well-being increased over time. In contrast, frequent online users who actively approach their emotions experienced no change in well-being, reporting highest levels of well-being overall. For patients who participate less intensively within the support community, coping style seems to outweigh effects of online participation; over time, patients who actively approached emotions experienced an increase in psychological well-being, whereas patients with a low score on emotional approach coping reported no change in depression and emotional well-being. ©Anika Batenburg, Enny Das.


Dinarello C.A.,Aurora University | Dinarello C.A.,Radboud University Nijmegen
Cancer and Metastasis Reviews | Year: 2010

The clinical successes of targeting angiogenesis provide a basis for trials of interleukin-1 (IL-1) blockade and particularly anti-IL-1β as an add-on therapy in human metastatic disease. In animal studies for over 20 years, IL-1 has been demonstrated to increase adherence of tumor cells to the endothelium in vitro, and administration of IL-1 to mice increases the number of metastatic colonies and tumor growth. Importantly, reducing endogenous IL-1 activity, particularly IL-1β, with the naturally occurring IL-1 receptor antagonist (IL-1Ra) reduces both metastasis as well as tumor burden. Inhibition of IL-1 activity prevents in vivo blood vessel formation induced by products released from hypoxic macrophages or vascular endothelial cell growth factor itself. Mice deficient in IL-1β do not form blood vessels in matrigels embedded with vascular endothelial cell growth factor or containing products of macrophages. Recombinant IL-1Ra (anakinra) has been administered to over 1,000 patients with septic shock resulting in a consistent reduction in all-cause 28-day mortality. Approved for treatment of rheumatoid arthritis, anakinra has a remarkable safety record. Anakinra resulted in decreased blood vessels in the pannus of affected joints in patients with rheumatoid arthritis. Neutralizing monoclonal antibodies to IL-1β and a soluble receptor to IL-1 are approved for treating chronic inflammatory diseases. Given the availability of three therapeutic agents for limiting IL-1 activity, the safety of blocking IL-1, and the clear benefit of blocking IL-1 activity in animal models of metastasis and angiogenesis, clinical trials of IL-1 blockade should be initiated, particularly as an add-on therapy of patients receiving antiangiogenesis-based therapies. © The Author(s) 2010.


Janner A.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2013

The affine extensions (there are 55 different ones) of the icosahedral group developed by T. Keef and R. Twarock of the York Centre for Complex Systems Analysis of the University of York [see in particular Keef et al. (2013). Acta Cryst. A69, 140-150], and applied to the investigation of the architecture of a number of icosahedral viruses, are here considered in the framework of molecular crystallography. The basic ideas of such molecular description involve positions with rational indices which approximate backbone positions in viral polypeptide and RNA chains. The test case of the Pariacoto virus suggests that the best-fit algorithm used in the York group's approach should be adapted to a more specific toolkit suited for the investigation of the architecture of icosahedral viruses. Typical problems which could be solved by means of such a toolkit are exemplified and put in the perspective of viral properties. © 2013 International Union of Crystallography Printed in Singapore-all rights reserved.


Stocchi F.,Institute for Research and Medical Care | Bloem B.R.,Radboud University Nijmegen
European Journal of Neurology | Year: 2013

Background and purpose: The Move for Change campaign is a three-part series of pan-European surveys designed by the European Parkinson's Disease Association (EPDA) to assess the impact that the EPDA Charter for People with Parkinson's disease (PD) has had since its launch in 1997. Here, we report results from the second survey, focusing on the third right of the Charter; that is, 'all patients have the right to have access to support services'. Although the level of evidence for different support services varies, it is important to ensure that patients can access services with clinically proven benefits. Methods: This survey comprised nine questions administered online via the EPDA and PD organization Web sites. Accessibility of support services was defined as 'services/medication/multidisciplinary healthcare professionals, etc. being available and on hand to patients when required'. Results: Neurologists and general practitioners (GPs) received highest accessibility results (90.0 and 87.0% of respondents, respectively), with moderate results for physiotherapists (68.0%) and PD organizations (72.0%) and lower results for PD specialist nurses (26.0%), occupational therapists (23.0%), and counselors (27.0%). Support provided by neurologists and PD specialists was considered to be 'very helpful' by 59.0 and 55.7%, respectively, whilst only 31.8% of respondents gave such favorable ratings to GPs. Funding of services was variable across Europe. Conclusions: These data demonstrate the challenges faced by PD patients in accessing the adequate care and support required throughout the course of their disease. These findings can assist healthcare professionals and policymakers in improving access to support services for patients and their families across Europe. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.


Falcke H.,Radboud University Nijmegen | Falcke H.,Max Planck Institute for Radio Astronomy | Markoff S.B.,University of Amsterdam
Classical and Quantum Gravity | Year: 2013

The center of our Galaxy hosts the best constrained supermassive black hole in the universe, Sagittarius A* (Sgr A*). Its mass and distance have been accurately determined from stellar orbits and proper motion studies, respectively, and its high-frequency radio, and highly variable near-infrared and x-ray emission originate from within a few Schwarzschild radii of the event horizon. The theory of general relativity (GR) predicts the appearance of a black hole shadow, which is a lensed image of the event horizon. This shadow can be resolved by very long baseline radio interferometry and test basic predictions of GR and alternatives thereof. In this paper we review our current understanding of the physical properties of Sgr A*, with a particular emphasis on the radio properties, the black hole shadow, and models for the emission and appearance of the source. We argue that the Galactic Center holds enormous potential for experimental tests of black hole accretion and theories of gravitation in their strong limits. © 2013 IOP Publishing Ltd.


Schalken J.A.,Radboud University Nijmegen
European Urology, Supplements | Year: 2015

Context: Benign prostatic hyperplasia (BPH) is classically understood to be a disturbance in prostate homeostasis, but the underlying questions of how and why this disturbance occurs have yet to be answered definitively. An increasing body of evidence points to inflammation as a central component of the pathogenic process of BPH. Objective: To review recent evidence regarding the association between histologic prostatic inflammation and the development and progression of BPH. Evidence acquisition: This article is based primarily on material presented at a satellite symposium entitled, "Inflammation and Prostatic Diseases: From Bench to Bedside," held during the 2015 annual meeting of the European Association of Urology in Madrid, Spain. Current data regarding the link between inflammation and BPH were reviewed. Evidence synthesis: Evidence from a canine model of BPH and human prostate tissue has confirmed the presence of inflammation as a component of BPH. Pronounced inflammation was observed in dogs with hormonally induced prostatic hyperplasia. Longitudinal biopsy indicated that the cell-mediated and humoral immune response was preceded by hyperplasia. In surgically treated human BPH specimens, high-level inflammation was significantly associated with prostate enlargement and symptom evolution. Current opinion is that chronic inflammation and endocrine changes lead to disturbed homeostasis and tissue damage or, alternatively, that abnormal stem cell expansion and disturbed homeostasis lead to chronic inflammation and endocrine changes. Either way, a "vicious cycle" is initiated that leads to hyperplasia with fibrosis and changes in prostate tissue composition. Conclusions: Increased insight into BPH pathogenesis indicates that restoring tissue endocrine metabolism and reducing chronic inflammation are prostate-specific targets for the treatment of BPH. Patient summary: Increasing insight into benign prostatic hyperplasia (BPH) pathogenesis indicates that restoring tissue endocrine metabolism and reducing chronic inflammation are prostate-specific targets for treatment of BPH. © 2015 European Association of Urology.


Verbeek F.,Radboud University Nijmegen | Schmaltz J.,Open University of the Netherlands
IEEE Transactions on Parallel and Distributed Systems | Year: 2011

The purpose of this comment is to show that Duato's condition for deadlock freedom is only sufficient and not necessary. We propose a fix to keep the condition necessary. The issue is subtle but essential: in a wormhole network worms necessarily do not intersect. © 2011 IEEE.


Van Dam N.M.,Radboud University Nijmegen | Heil M.,CINVESTAV
Journal of Ecology | Year: 2011

Plants mediate multiple interactions between below-ground (BG) and above-ground (AG) heterotrophic communities that have no direct physical contact. These interactions can be positive or negative from the perspective of each player, can go from the BG to the AG community or vice versa, and comprise representatives of different phyla. Here we highlight emerging general patterns and discuss future research directions. Ecologists initially postulated that root herbivores induce general stress responses, which increase the levels of primary (nutritional) compounds in the undamaged plant compartment and thereby facilitate future attack by AG herbivores. However, damage can also reduce the levels of primary compounds or increase contents of secondary (defensive) metabolites. Both effects may cause resistance phenotypes that play an important role in mediating BG-AG interactions. Systemically induced resistance does not only affect other herbivores but also pathogens in the AG and BG compartment and may inhibit beneficial organisms such as natural enemies of herbivores, microbial root symbionts and pollinators. Conversely, symbiotic mutualists such as mycorrhiza and rhizobia may affect AG and BG defence levels. Finally, BG-AG interactions may be costly if they impede optimal defence strategies in the undamaged compartment. Synthesis. In order to better understand the adaptive value of BG-AG induced responses for the players involved and to identify the driving evolutionary forces, we need a better integration of studies at the community level with experiments on model systems that allow unravelling the genetic and physiological mechanisms of BG-AG interactions. Experiments preferably should be carried out at realistic densities and using the natural temporal sequence at which the various associations are established, because we can expect plants to be adapted only to events that are common over evolutionary time spans. Detailed mechanistic knowledge will help to reproduce relevant interactions in experiments that study multiple species in the field. This step will ultimately allow us to evaluate the importance of plant-mediated interactions between BG and AG communities for the fitness of the species involved and for the structuring of natural communities. © 2011 The Authors. Journal of Ecology © 2011 British Ecological Society.


van den Brand J.A.,Radboud University Nijmegen
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2011

Chronic kidney disease (CKD) is defined as the presence of kidney damage, albuminuria or a reduction in glomerular filtration rate (GFR). A GFR <60 mL/min/1.73 m(2) alone is sufficient to diagnose CKD Stages III-V. Recently, the new chronic kidney disease epidemiology collaboration (CKD-EPI) equation was introduced. It has been suggested to result in higher estimated glomerular filtration rates (eGFRs) than the Modification of Diet in Renal Disease (MDRD(4)) formula. Here, we assess consequences of introducing the CKD-EPI equation in a West European Caucasian population. Data were obtained from 6097 Caucasian participants of the Nijmegen Biomedical Study (2823 males and 3274 females). Serum creatinine values were determined using the Jaffe method, calibrated against mass spectrometry and were used to calculate eGFR(MDRD4) and eGFR(CKD-EPI). Demographic data, health status and information on medication use for all participants was obtained with a postal questionnaire. The introduction of the CKD-EPI equation changed the curve of eGFR by age, with higher values in the younger age groups and a steeper decline of eGFR with ageing. As a consequence, younger people were more often classified to a higher GFR stage and older people, especially males, to a lower GFR stage. In comparison with the MDRD(4) formula, the CKD-EPI equation leads to higher estimates of GFR in young people and lower estimates in the elderly. On a population level, this may lead to higher estimates of kidney function. However, in routine clinical practice where the population is predominantly elderly, the opposite may be true. The introduction of eGFR(CKD-EPI) necessitates reconsidering the definition of CKD. We suggest introducing age-dependent threshold values and/or the use of urinary albumin excretion to improve risk stratification.


Van Velzen S.,Radboud University Nijmegen | Farrar G.R.,New York University
Astrophysical Journal | Year: 2014

We report an observational estimate of the rate of stellar tidal disruption flares (TDFs) in inactive galaxies based on a successful search for these events among transients in galaxies using archival Sloan Digital Sky Survey (SDSS) multi-epoch imaging data (Stripe 82). This search yielded 186 nuclear flares in galaxies, 2 of which are excellent TDF candidates. Because of the systematic nature of the search, the very large number of galaxies, the long time of observation, and the fact that non-TDFs were excluded without resorting to assumptions about TDF characteristics, this study provides an unparalleled opportunity to measure the TDF rate. To compute the rate of optical stellar tidal disruption events, we simulate our entire pipeline to obtain the efficiency of detection. The rate depends on the light curves of TDFs, which are presently still poorly constrained. Using only the observed part of the SDSS light curves gives a model-independent upper limit to the optical TDF rate, Ṅ < 2 × 10-4 yr-1 galaxy-1 (90% CL), under the assumption that the SDSS TDFs are representative examples.We develop three empirical models of the light curves based on the two SDSS light curves and two more recent and better-sampled Pan-STARRS TDF light curves, leading to our best estimate of the rate: ṄTDF = (1.5-2.0) -1.3 +2.7 ×10-5 yr-1 galaxy-1. We explore the modeling uncertainties by considering two theoretically motivated light curve models, as well as two different relationships between black hole mass and galaxy luminosity, and two different treatments of the cutoff in the visibility of TDFs at large MBH. From this we conclude that these sources of uncertainty are not significantly larger than the statistical ones. Our results are applicable for galaxies hosting black holes with mass in the range of a few 106-10 8M⊙, and translates to a volumetric TDF rate of (4-8)×10-8±0.4 yr-1 Mpc-3, with the statistical uncertainty in the exponent. © 2014. The American Astronomical Society. All rights reserved.


Riksen N.P.,Radboud University Nijmegen
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

Objective - Although the role of monocytes in the pathogenesis of atherosclerosis is well established, the persistent vascular inflammation remains largely unexplained. Recently, our group reported that stimulation of monocytes with various microbial products can induce a long-lasting proinflammatory phenotype via epigenetic reprogramming, a process termed trained immunity. We now hypothesize that oxidized low-density lipoprotein (oxLDL) also induces a long-lasting proinflammatory phenotype in monocytes, which accelerates atherosclerosis by proinflammatory cytokine production and foam cell formation. Approach And Results - Isolated human monocytes were exposed for 24 hours to medium or oxLDL. After washing and resting for 6 days, the cells were exposed to toll-like receptor 2 and 4 agonists. Pre-exposure to oxLDL increased mRNA expression and protein formation on toll-like receptor 2 and 4 stimulation of several proatherogenic proteins, including interleukin-6, interleukin-18, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein 1, and matrix metalloproteinase 2 and 9. In addition, foam cell formation was enhanced after oxLDL exposure, which was associated with an upregulation of scavenger receptors CD36 and scavenger receptor-A and downregulation of ATP-binding cassette transporters, ABCA1 and ABCG1. Chromatin immunoprecipitation performed 6 days after oxLDL stimulation demonstrated increased trimethylation of lysine 4 at histone 3 in promoter regions of tnfα, il-6, il-18, mcp-1, mmp2, mmp9, cd36, and sr-a. Finally, pretreatment of the monocytes with the histone methyltransferase inhibitor methylthioadenosine completely prevented the oxLDL-induced long-lasting proinflammatory phenotype. Conclusions - Brief exposure of monocytes to a low concentration of oxLDL induces a long-lasting proatherogenic macrophage phenotype via epigenetic histone modifications, characterized by increased proinflammatory cytokine production and foam cell formation. © 2014 American Heart Association, Inc.


Paulus M.,Ludwig Maximilians University of Munich | Fikkert P.,Radboud University Nijmegen
Journal of Cognition and Development | Year: 2014

Language acquisition is a process embedded in social routines. Despite considerable attention in research to its social nature, little is known about developmental differences in the relative priority of certain social cues over others during early word learning. Employing an eye-tracking paradigm, we presented 14-month-old infants, 24-month-old infants, and adults with movies in which an actor repeatedly gazed at one and pointed to the other of two objects while presenting them with a novel word. The results show that the 14-month-old infants pay more attention to a model's eye gaze when learning to map a novel word to a referent, whereas 24-month-old infants and adults rely more on pointing cues. Our results provide evidence for a developmental change in the relative priority of pointing versus eye-gazing cues in language acquisition. © 2014 Taylor and Francis Group, LLC.


van Houtum H.,Radboud University Nijmegen
Environment and Planning D: Society and Space | Year: 2010

Over the last few years, the global face of the EU has been changing. The EU is spinning a global border web with regard to the battle against irregular migration. At the borders of the EU, a powerful and security-obsessed distinction between travellers is increasingly being constructed between the travellers who 'belong to' the EU and those who do not, based on the fate of birth. To this end, the EU has composed a so-called 'white and black' Schengen list, recently relabelled a 'positive and negative' list, which is used as a criterion for visa applications. What is striking is that on the negative list a significantly high number of Muslim and developing states are listed. Hence, there is an implicit, strong inclination to use this list not only as a tool to guarantee security in physical terms or in terms of 'Western' identity protection but also as a means of keeping the world's poorest out. Such global apartheid geopolitics-loaded with rhetoric on selective access, burden, and masses-provokes the dehumanisation and illegalisation of the travel of those who were born in what the EU has defined as the 'wrong country', the wastable and deportable lives from countries on the negative list. Such un-authorised travelling is increasingly dangerous as the high death toll suggests. It has led to a new and yet all too familiar geopolitical landscape in Europe, a scene many of us hope to never see again in postwar Europe, a landscape of barbed wire surveillance and camps. And hence, the EU-which started out as a means to produce a zone of peace and comfort ruled by law and order-has now in its self-proclaimed war on illegal migrants created a border industry that coconstructs more, not less, 'illegality', xenophobia, and fear: the EU as a global border machine. © 2010 Pion Ltd and its Licensors.


Voss T.S.,Swiss Tropical and Public Health Institute | Voss T.S.,University of Basel | Bozdech Z.,Nanyang Technological University | Bartfai R.,Radboud University Nijmegen
Current Opinion in Microbiology | Year: 2014

Malaria parasites run through a complex life cycle in the vertebrate host and mosquito vector. This not only requires tightly controlled mechanisms to govern stage-specific gene expression but also necessitates effective strategies for survival under changing environmental conditions. In recent years, the combination of different -omics approaches and targeted functional studies highlighted that Plasmodium falciparum blood stage parasites use heterochromatin-based gene silencing as a unifying strategy for clonally variant expression of hundreds of genes. In this article, we describe the epigenetic control mechanisms that mediate alternative expression states of genes involved in antigenic variation, nutrient uptake and sexual conversion and discuss the relevance of this strategy for the survival and transmission of malaria parasites. © 2014.


de Pauw B.E.,Radboud University Nijmegen | Viscoli C.,University of Genoa
Journal of Antimicrobial Chemotherapy | Year: 2011

The management of invasive fungal disease in the immunocompromised host is complex and requires the specialized knowledge of physicians whose primary interest is actually the underlying disease rather than infectious complications. This Supplement aims to provide these physicians with some tools that may help to guide them through the maze of suspicion that an invasive fungal disease is present by offering an integrated care pathway of rational patient management. Such pathways will inevitably vary in detail in different centres and depend for their success on the presence of multidisciplinary teams and an explicit agreement on at least the minimum requirements for effective management. The integrated care pathways presented constitute an objective instrument to allow regular audits for recognizing opportunities to change practice if and when weaknesses are identified. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


For the past decade, docetaxel has remained the global standard of care for frontline treatment of metastatic castration-resistant prostate cancer (mCRPC). Until recently, there were limited options for patients with mCRPC following docetaxel failure or resistance, but now the approved treatment choices for these patients have expanded to include abiraterone acetate, cabazitaxel and enzalutamide. Additionally, the radioactive therapeutic agent radium-223 dichloride has been recently approved in patients with CRPC with bone metastases. Although each of these agents has been shown to convey significant survival benefit as a monotherapy, preclinical findings suggest that combining such innovative strategies with traditional treatments may achieve additive or synergistic effects, further augmenting patient benefit. This review will discuss the transformation of the post-docetaxel space in mCRPC, highlighting the spectrum of newly approved agents in this setting in the USA and the European Union, as well as summarizing treatments with non-chemotherapeutic mechanisms of action that have demonstrated promising results in recent phase 3 trials. Lastly, this review will address the potential of combinatorial regimens in mCRPC, including the pairing of novel immunotherapeutic approaches with chemotherapy, radiotherapy or androgen ablation.


van der Linden M.,Radboud University Nijmegen
Cochrane database of systematic reviews (Online) | Year: 2011

Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin (hCG), which is produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques (ART) the progesterone or hCG levels, or both, are low and the natural process is insufficient, so the luteal phase is supported with either progesterone, hCG or gonadotropin releasing hormone (GnRH) agonists. Luteal phase support improves implantation rate and thus pregnancy rates but the ideal method is still unclear. This is an update of a Cochrane Review published in 2004 (Daya 2004). To determine the relative effectiveness and safety of methods of luteal phase support in subfertile women undergoing assisted reproductive technology. We searched the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects (DARE), LILACS, conference abstracts on the ISI Web of Knowledge, OpenSigle for grey literature from Europe, and ongoing clinical trials registered online. The final search was in February 2011. Randomised controlled trials of luteal phase support in ART investigating progesterone, hCG or GnRH agonist supplementation in in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. Quasi-randomised trials and trials using frozen transfers or donor oocyte cycles were excluded. We extracted data per women and three review authors independently assessed risk of bias. We contacted the original authors when data were missing or the risk of bias was unclear. We entered all data in six different comparisons. We calculated the Peto odds ratio (Peto OR) for each comparison. Sixty-nine studies with a total of 16,327 women were included. We assessed most of the studies as having an unclear risk of bias, which we interpreted as a high risk of bias. Because of the great number of different comparisons, the average number of included studies in a single comparison was only 1.5 for live birth and 6.1 for clinical pregnancy.Five studies (746 women) compared hCG versus placebo or no treatment. There was no evidence of a difference between hCG and placebo or no treatment except for ongoing pregnancy: Peto OR 1.75 (95% CI 1.09 to 2.81), suggesting a benefit from hCG. There was a significantly higher risk of ovarian hyperstimulation syndrome (OHSS) when hCG was used (Peto OR 3.62, 95% CI 1.85 to 7.06).There were eight studies (875 women) in the second comparison, progesterone versus placebo or no treatment. The results suggested a significant effect in favour of progesterone for the live birth rate (Peto OR 2.95, 95% CI 1.02 to 8.56) based on one study. For clinical pregnancy (CPR) the results also suggested a significant result in favour of progesterone (Peto OR 1.83, 95% CI 1.29 to 2.61) based on seven studies. For the other outcomes the results indicated no difference in effect.The third comparison (15 studies, 2117 women) investigated progesterone versus hCG regimens. The hCG regimens were subgrouped into comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. The results did not indicate a difference of effect between the interventions, except for OHSS. Subgroup analysis of progesterone versus progesterone + hCG showed a significant benefit from progesterone (Peto OR 0.45, 95% CI 0.26 to 0.79).The fourth comparison (nine studies, 1571 women) compared progesterone versus progesterone + oestrogen. Outcomes were subgrouped by route of administration. The results for clinical pregnancy rate in the subgroup progesterone versus progesterone + transdermal oestrogen suggested a significant benefit from progesterone + oestrogen. There was no evidence of a difference in effect for other outcomes.


Franssen P.M.,Radboud University Nijmegen | Imholz B.P.,Twee Steden Hospital
Blood Pressure Monitoring | Year: 2010

We report on the validation of the new generation Mobil-O-Graph 24/48h ambulatory blood pressure monitor according to the criteria of the European Society of Hypertension. In 15 individuals participating in phase I for systolic pressure, all 45 measures differed less than 15mmHg, 43 and 33 out of 45 differed less than 10 and 5mmHg. As for diastolic pressures even better scores were reached when the device passed the EHS score.In phase II, data were collected in an additional 18 individuals leaving a total of 33 individuals and 99 measures. The phase counts the achieved percentages of two or three measures per individual within 15, 10 and 5mmHg limits. Systolic pressures exceeded the required 95, 80 and 65% for 15, 10 and 5mmHg differences with values of 98, 94 and 71%, respectively. As again for diastolic pressure the values were even better, the device passed phase II also.Thus, all phases of the European Society of Hypertension procedure were passed and the results of this study can recommend the use of the Mobil-O-Graph new generation ambulatory blood pressure monitor device in clinical practice. © Lippincott Williams & Wilkins.


Lappenschaar M.,Radboud University Nijmegen
AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium | Year: 2012

Multimorbidity, i.e., the presence of multiple diseases within one person, is a significant health-care problem for western societies: diagnosis, prognosis and treatment in the presence of of multiple diseases can be complex due to the various interactions between diseases. A literature review reveals that there is a variety of definitions that describe different concepts with respect to multimorbidity, both for the cause of multimorbidity as well as the implications of multimorbidity. To be able to aid computerized decision support systems within patient care, e.g. electronic clinical guidelines that can be personalized given the patient's problems, these multimorbidity aspects need to be defined rigorously in a formal language. In this paper, we employ causal Bayesian networks to define and analyze a novel framework that can be used to model a spectrum of aspects related to multimorbidity. We conclude that this framework provides a solid basis for modeling interactions between multiple diseases.


When Plasmodium vivax tertian malaria was prevalent in The Netherlands, the use of therapeutic malaria for the treatment of neurosyphilis patients presented an opportunity for biological studies of the parasite's behaviour, in healthy volunteers. One unexplained phenomenon was the long latency between natural exposure to a single infected mosquito and the appearance of clinical signs (average 8 months). Dutch studies with volunteers and syphilis patients, suggested that hundreds of sporozoites transmitted by several mosquito bites were enough to provoke an early attack, known from tropical vivax-malaria. Sporozoites appeared to be programmed either to delay their pre-erythrocytic development or to proceed to an early attack within three weeks. The number of infectious bites also determined the relapse rate and the number of relapses after a primary attack. Analyses of primary cases and relapses from the previous year were used to predict the incidence for the next year. These historic findings fit well with recent studies on genotyping of blood stages during primary attacks and relapses. External factors (i.e. the milieu inside the human host) may trigger hypnozoites to reactivate, but predetermined periods of latency should also be considered. © 2013 Verhave; licensee BioMed Central Ltd.


Gershlick A.H.,University of Leicester | Banning A.P.,Oxford Radcliffe Hospitals | Myat A.,Kings College London | Verheugt F.W.A.,Radboud University Nijmegen | Gersh B.J.,Mayo Medical School
The Lancet | Year: 2013

In the past ten years, primary percutaneous coronary intervention (PCI) has replaced thrombolysis as the revascularisation strategy for many patients presenting with ST-segment elevation myocardial infarction (STEMI). However, delivery of primary PCI within evidence-based timeframes is challenging, and health-care provision varies substantially worldwide. Consequently, even with the ideal circumstances of rapid initial diagnosis, long transfer delays to the catheter laboratory can occur. These delays are detrimental to outcomes for patients and can be exaggerated by variations in timing of patients' presentation and diagnosis. In this Series paper we summarise the value of immediate out-of-hospital thrombolysis for STEMI, and reconsider the potential therapeutic interface with a contemporary service for primary PCI. We review recent trial data, and explore opportunities for optimisation of STEMI outcomes with a pharmacoinvasive approach.


Simmer F.,Radboud University Nijmegen
Epigenetics : official journal of the DNA Methylation Society | Year: 2012

Aberrant DNA methylation often occurs in colorectal cancer (CRC). In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions (DMRs) in 24 tumors and matched normal colon samples. In total, 2687 frequently hypermethylated and 468 frequently hypomethylated regions were identified, which include potential biomarkers for CRC diagnosis. Hypermethylation in the tumor samples was enriched at CpG islands and gene promoters, while hypomethylation was distributed throughout the genome. Using epigenetic data from human embryonic stem cells, we show that frequently hypermethylated regions coincide with bivalent loci in human embryonic stem cells. DNA methylation is commonly thought to lead to gene silencing; however, integration of publically available gene expression data indicates that 75% of the frequently hypermethylated genes were most likely already lowly or not expressed in normal tissue. Collectively, our study provides genome-wide DNA methylation maps of CRC, comprehensive lists of DMRs, and gives insights into the role of aberrant DNA methylation in CRC formation.


Frencken J.E.,Radboud University Nijmegen
Dental Materials | Year: 2010

Dental caries is the most prevalent non-communicable disease in the world. Its management in high-income countries over the last four decades has resulted in relatively low caries prevalence in child and adolescent populations. In low- and middle-income countries, caries management is virtually non-existent and this may lead to serious physical and mental complications, particularly in children. Toothache is predominantly treated by extracting the cavitated tooth. Absence of restorative oral care is partly due to the copying from high-income countries, of restorative treatment reliant on electrically driven equipment and often inappropriate for use in many low- and middle-income countries. Atraumatic Restorative Treatment (ART), which does not rely on electrically driven equipment, has yielded good results over the last two decades. ART uses hand instruments and high-viscosity glass-ionomers. Its introduction into public oral healthcare systems has been piloted in several countries. Initial short-term results show that the introduction of ART, using high-viscosity glass-ionomers, has increased the ratio of restorations to extractions. Moreover, the percentage of ART restorations in relation to the total number of restorations placed increased steeply after its introduction and has remained high. However, ART introduction faced a few barriers, the most important being high patient workloads and the absence of a constant supply of dental instruments and glass-ionomers. High-viscosity glass-ionomer has become an essential element in public oral healthcare systems, particularly in those operating inadequately. © 2009 Academy of Dental Materials.


Scharenborg O.,Radboud University Nijmegen
Journal of the Acoustical Society of America | Year: 2010

Evidence that listeners, at least in a laboratory environment, use durational cues to help resolve temporarily ambiguous speech input has accumulated over the past decades. This paper introduces Fine-Tracker, a computational model of word recognition specifically designed for "tracking" fine-phonetic information in the acoustic speech signal and using it during word recognition. Two simulations were carried out using real speech as input to the model. The simulations showed that the Fine-Tracker, as has been found for humans, benefits from durational information during word recognition, and uses it to disambiguate the incoming speech signal. The availability of durational information allows the computational model to distinguish embedded words from their matrix words (first simulation), and to distinguish word final realizations of [s] from word initial realizations (second simulation). Fine-Tracker thus provides the first computational model of human word recognition that is able to extract durational information from the speech signal and to use it to differentiate words. © 2010 Acoustical Society of America.


Jacobs B.,Radboud University Nijmegen
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

The paper investigates non-deterministic, probabilistic and quantum walks, from the perspective of coalgebras and monads. Non-deterministic and probabilistic walks are coalgebras of a monad (powerset and distribution), in an obvious manner. It is shown that also quantum walks are coalgebras of a new monad, involving additional control structure. This new monad is also used to describe Turing machines coalgebraically, namely as controlled 'walks' on a tape. © 2011 Springer-Verlag.


Bojak I.,Radboud University Nijmegen | Liley D.T.J.,Swinburne University of Technology
PLoS Computational Biology | Year: 2010

By modelling the average activity of large neuronal populations, continuum mean field models (MFMs) have become an increasingly important theoretical tool for understanding the emergent activity of cortical tissue. In order to be computationally tractable, long-range propagation of activity in MFMs is often approximated with partial differential equations (PDEs). However, PDE approximations in current use correspond to underlying axonal velocity distributions incompatible with experimental measurements. In order to rectify this deficiency, we here introduce novel propagation PDEs that give rise to smooth unimodal distributions of axonal conduction velocities. We also argue that velocities estimated from fibre diameters in slice and from latency measurements, respectively, relate quite differently to such distributions, a significant point for any phenomenological description. Our PDEs are then successfully fit to fibre diameter data from human corpus callosum and rat subcortical white matter. This allows for the first time to simulate long-range conduction in the mammalian brain with realistic, convenient PDEs. Furthermore, the obtained results suggest that the propagation of activity in rat and human differs significantly beyond mere scaling. The dynamical consequences of our new formulation are investigated in the context of a well known neural field model. On the basis of Turing instability analyses, we conclude that pattern formation is more easily initiated using our more realistic propagator. By increasing characteristic conduction velocities, a smooth transition can occur from self-sustaining bulk oscillations to travelling waves of various wavelengths, which may influence axonal growth during development. Our analytic results are also corroborated numerically using simulations on a large spatial grid. Thus we provide here a comprehensive analysis of empirically constrained activity propagation in the context of MFMs, which will allow more realistic studies of mammalian brain activity in the future. © 2010 Bojak, Liley.


Hessels D.,NovioGendix BV | Schalken J.A.,Radboud University Nijmegen
Asian Journal of Andrology | Year: 2013

Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection, one of its main drawbacks is its lack of specificity. As a consequence, many men undergo unnecessary biopsies or treatments for indolent tumours. PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour. Since PCa is a heterogeneous disease, a panel of tumour markers is fundamental for a more precise diagnosis. Several biomarkers are promising due to their specificity for the disease in tissue. However, tissue is unsuitable as a possible screening tool. Since urine can be easily obtained in a non-invasive manner, it is a promising substrate for biomarker testing. This article reviews the biomarkers for the non-invasive testing of PCa in urine. © 2013 AJA, SIMM & SJTU. All rights reserved.


Seyedmousavi S.,Radboud University Nijmegen
Expert review of anti-infective therapy | Year: 2013

Voriconazole and posaconazole are extended-spectrum triazoles recommended for treatment, prophylaxis and salvage therapy of Aspergillus diseases. Over the past decade many papers have emerged supporting the use of therapeutic drug monitoring (TDM) for azole antifungals. TDM is used to tailor the exposure of a specific drug to the individuals to optimize treatment response and minimize side effects. We reviewed the pharmacokinetics and pharmacodynamics (PK-PD) characteristics of voriconazole and posaconazole. We present the available evidence on target concentrations defining maximal efficacy and minimal toxicity. Finally we provide some practical recommendations how to best perform TDM in clinical practice.


Kulkarni S.A.,Technical University of Delft | McGarrity E.S.,Technical University of Delft | Meekes H.,Radboud University Nijmegen | Ter Horst J.H.,Technical University of Delft
Chemical Communications | Year: 2012

We show that, in a controlled and reproducible way, specific solvents lead to specific polymorphic forms of isonicotinamide. We argue on the basis of Raman and FTIR spectroscopy that the hydrogen bonding in solution kinetically drives the nucleation towards a specific form. This generally may lead to good understanding and control of polymorphism and crystal nucleation. © The Royal Society of Chemistry 2012.


Muradian R.,Radboud University Nijmegen | Walter M.,Autonomous University of Barcelona | Martinez-Alier J.,Autonomous University of Barcelona
Global Environmental Change | Year: 2012

This introductory paper to the special section of Global Environmental Change entitled "Global transformations, social metabolism and the dynamics of socio-environmental conflicts" argues that the emergence of new global economic centers is inducing a major expansion in the global social metabolism-the flows of energy and materials into the world economy -, a transformation in the systems for the extraction and provision of natural resources, as well as setting the conditions for socio-environmental conflicts at the commodity frontiers, particularly in areas with a dense human occupation of the territory. We point out that we are currently experiencing global transformations that constitute the beginning of a new historical phase of modern capitalism. The aim of the paper is to draw an overall picture of such transformations, to discuss some of their implications for resource-rich countries, particularly in Latin America and Africa, and by doing so to provide an analytical framework that allow us to make explicit the linkages between the different papers that compose the special section. © 2012 Elsevier Ltd.


Dugaev V.K.,Rzeszow University of Technology | Katsnelson M.I.,Radboud University Nijmegen
Physical Review B - Condensed Matter and Materials Physics | Year: 2014

We discuss the role of spin-flip scattering of electrons from the magnetized edges in graphene nanoribbons. The spin-flip scattering is associated with strong fluctuations of the magnetic moments at the edge. Using the Boltzmann equation approach, which is valid for not too narrow nanoribbons, we calculate the spin-relaxation time in the case of Berry-Mondragon and zigzag graphene edges. We also consider the case of ballistic nanoribbons characterized by very long momentum relaxation time in the bulk, when the main source of momentum and spin relaxation is the spin-dependent scattering at the edges. We found that in the case of zigzag edges, an anomalous spin diffusion is possible, which is related to very weak spin-flip scattering of electrons gliding along the nanoribbon edge. © 2014 American Physical Society.


Van Der Heijden A.G.,Radboud University Nijmegen
Archivos Espanoles de Urologia | Year: 2013

Alterations in DNA methylation have been described in human cancer for more than thirty years now. Since the last decade DNA methylation gets more and more important in cancer research. In this review the different alterations of DNA methylation are discussed in testicular germ cell tumours, Wilms' tumours, renal cell carcinomas, urothelial cell carcinomas of the bladder and adenocarcinomas of the prostate. Eventually, the potential use in diagnostics, prognostics and therapy are discussed.


Chaturvedi A.A.,Radboud University Nijmegen
The British journal of surgery | Year: 2013

Postoperative adhesion formation is a common consequence of abdominal surgery, and constitutes a major source of morbidity and mortality. This study evaluated an ultrapure alginate-based antiadhesive barrier gel. Experiments were performed in a rat model with caecal abrasion and peritoneal side wall excision. The primary endpoint was the incidence of adhesions at 14 days after surgery. In experiment 1 (24 rats), animals treated with alginate gel were compared with controls that had no antiadhesive barrier. In experiment 2 (42 rats), alginate gel was compared with sodium hyaluronate carboxymethyl cellulose (HA/CMC) membrane and with no antiadhesive barrier. To check for any remote action of the gel, in experiment 3 (45 rats) application of alginate gel to the ipsilateral versus contralateral side of injury was compared with no antiadhesive barrier. In experiment 1, ultrapure alginate gel reduced the incidence of adhesions from eight of 12 in control animals to one in 12 (P = 0·009). Tissue healing assessed by histology was similar in both groups. In experiment 2, ultrapure alginate gel and HA/CMC membrane showed similar antiadhesive effectiveness, reducing the incidence of adhesions from ten of 14 rats in the control group to three of 14 (P = 0·021) and two of 14 (P = 0·006) respectively. In experiment 3, ultrapure alginate gel reduced the incidence of adhesions at the site of direct application (1 of 15) compared with controls (13 of 15; P = 0·001), but not if applied remotely (9 of 15; P = 0·214). Ultrapure alginate gel decreased the incidence of postoperative adhesion formation in this rat model. © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.


Schulze H.-J.,National Institute of Nuclear Physics, Italy | Rijken T.,Radboud University Nijmegen
Physical Review C - Nuclear Physics | Year: 2011

We perform Brueckner-Hartree-Fock calculations of hypernuclear matter employing the recent Nijmegen ESC08 hyperon-nucleon potentials, provide useful parametrizations of the numerical results, and compute the structure of hyperon (neutron) stars within this approach. Very low maximum masses below 1.4 solar masses are found. © 2011 American Physical Society.


Schouten G.,University Utrecht | Leroy P.,Radboud University Nijmegen | Glasbergen P.,University Utrecht
Ecological Economics | Year: 2012

The democratic quality of private multi-stakeholder governance is an important subject of academic and political debate. On the one hand, private multi-stakeholder arrangements are seen as a way of democratizing international environmental governance. On the other hand, the democratic potential of these arrangements has been heavily criticized and interpreted as a privatization of what should be public. To nuance this debate, this paper assesses the democratic potential of one specific type of arrangement: Roundtables. These Roundtables are presented as being based on a deliberative democratic rationale. This paper therefore assesses the deliberative capacity of the Roundtables on Responsible Soy and Sustainable Palm Oil and shows to what extent the communicative processes in these Roundtables are inclusive, consequential and authentic. This paper concludes that the Roundtable model tends to fall short on two criteria of deliberative democracy: inclusiveness (of actors and discourses) and consequentiality. © 2012 Elsevier B.V.


Rutten R.,University of Tilburg | Boekema F.,Radboud University Nijmegen
Regional Studies | Year: 2012

Rutten R. and Boekema F. From learning region to learning in a socio-spatial context, Regional Studies. Conceptually ambiguous and too intimately connected to regional innovation policy, the 'learning region' failed to develop into a mature concept. This paper and the special issue it introduces take stock of advances in the learning region literature of the past twenty years. It then suggests a different approach to conceptualizing the relation between space and learning. Based on an understanding of learning as social interaction among individuals, the paper and special issue suggest a relational approach to explaining learning in a socio-spatial context. This approach augments the Territorial Innovation Models literature that too often reduces relational concepts, such as social capital, to stylized regional characteristics. © 2012 Copyright Regional Studies Association.


Fernandez I.,Complutense University of Madrid | Bickelhaupt F.M.,VU University Amsterdam | Bickelhaupt F.M.,Radboud University Nijmegen
Chemical Society Reviews | Year: 2014

In this Tutorial Review, we make the point that a true understanding of trends in reactivity (as opposed to measuring or simply computing them) requires a causal reactivity model. To this end, we present and discuss the Activation Strain Model (ASM). The ASM establishes the desired causal relationship between reaction barriers, on one hand, and the properties of reactants and characteristics of reaction mechanisms, on the other hand. In the ASM, the potential energy surface ΔE(ζ) along the reaction coordinate ζ is decomposed into the strain ΔEstrain(ζ) of the reactants that become increasingly deformed as the reaction proceeds, plus the interaction ΔEint(ζ) between these deformed reactants, i.e., ΔE(ζ) = ΔEstrain(ζ) + ΔE int(ζ). The ASM can be used in conjunction with any quantum chemical program. An analysis of the method and its application to problems in organic and organometallic chemistry illustrate the power of the ASM as a unifying concept and a tool for rational design of reactants and catalysts. This journal is © the Partner Organisations 2014.


Coenen A.,Radboud University Nijmegen
International Journal of Psychophysiology | Year: 2012

The shape of evoked potentials is influenced by the level of vigilance, varying with sleep-wake states. In this paper the shape of auditory evoked potentials is modelled by taking two factors, both modulating the underlying neuronal substrate, into account: 'sensory gating' and 'neuronal firing mode'. Under low levels of vigilance sensory gating reduces the amount of neuronal activity reaching the cortical centres. Due to a rise in hyperpolarisations of thalamocortical neurons associated with an increasing depth of sleep, stimulus evoked primary and secondary excitations, seen as correlates of the N1 and N2 waves of the evoked potential, become smaller. Heightened hyperpolarisations also change the spontaneous activity of neurons from the 'tonic' firing mode of wakefulness into the 'burst-pause' firing mode of sleep. The large P220 complex together with the N350 and N550 waves in sleep are caused by the stimulus induced triggering of pauses and bursting of neurons. The results of this modelling experiment confirm the view that sleep-specific components such as P220, N350 and N550 are waves that facilitate and protect sleep, whereas the wake-specific components N1, P2-P3 and N2 have perceptual-cognitive functions. In particular the wake P2-P3 wave is sensitive to cognitive functions, such as attention. Based on the modelling results it is suggested that component negativities, expressed in N1, N2 and N350, reflect excitatory processes, whereas positivity in P2-P3 and P220 is a correlate of inhibitory processes. Hence, the large P3 in an attended condition is also interpreted as an inhibitory process suppressing irrelevant information, facilitation the saliency of relevant information. © 2011 Elsevier B.V..


Donken C.C.,Radboud University Nijmegen
Cochrane database of systematic reviews (Online) | Year: 2012

The annual incidence of ankle fractures is 122 per 100,000 people. They usually affect young men and older women. The question of whether surgery or conservative treatment should be used for ankle fractures remains controversial. To assess the effects of surgical versus conservative interventions for treating ankle fractures in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2012 Issue 1), MEDLINE, EMBASE, CINAHL and the WHO International Clinical Trials Registry Platform and Current Controlled Trials. Date of last search: 6 February 2012. Randomised and quasi-randomised controlled clinical studies comparing surgical and conservative treatments for ankle fractures in adults were included. Two review authors independently performed study selection, risk of bias assessment and data extraction. Authors of the included studies were contacted to obtain original data. Three randomised controlled trials and one quasi-randomised controlled trial were included. These involved a total of 292 participants with ankle fractures. All studies were at high risk of bias from lack of blinding. Additionally, loss to follow-up or inappropriate exclusion of participants put two trials at high risk of attrition bias. The trials used different and incompatible outcome measures for assessing function and pain. Only limited meta-analysis was possible for early treatment failure, some adverse events and radiological signs of arthritis.One trial, following up 92 of 111 randomised participants, found no statistically significant differences between surgery and conservative treatment in patient-reported symptoms (self assessed ankle "troubles": 11/43 versus 14/49; risk ratio (RR) 0.90, 95% CI 0.46 to 1.76) or walking difficulties at seven years follow-up. One trial, reporting data for 31 of 43 randomised participants, found a statistically significantly better mean Olerud score in the surgically treated group but no difference between the two groups in pain scores after a mean follow-up of 27 months. A third trial, reporting data for 49 of 96 randomised participants at 3.5 years follow-up, reported no difference between the two groups in a non-validated clinical score.Early treatment failure, generally reflecting the failure of closed reduction (criteria not reported in two trials) probably or explicitly leading to surgery in patients allocated conservative treatment, was significantly higher in the conservative treatment group (2/116 versus 19/129; RR 0.18, 95% CI 0.06 to 0.54). Otherwise, there were no statistically significant differences between the two groups in any of the reported complications. Pooled results from two trials of participants with radiological signs of osteoarthritis at averages of 3.5 and 7.0 years follow-up showed no between-group differences (44/66 versus 50/75; RR 1.05, 95% CI 0.83 to 1.31). There is currently insufficient evidence to conclude whether surgical or conservative treatment produces superior long-term outcomes for ankle fractures in adults. The identification of several ongoing randomised trials means that better evidence to inform this question is likely to be available in future.


Gordon A.M.,Columbia University | Bleyenheuft Y.,Catholic University of Louvain | Steenbergen B.,Radboud University Nijmegen
Developmental Medicine and Child Neurology | Year: 2013

Unilateral spastic cerebral palsy, caused by damage to the developing central nervous system, is characterized by motor impairments mainly lateralized to one side of the body, with hand impairments greatly contributing to functional limitations. The integrity of the motor areas and the corticospinal tract (CST) is often compromised. The specific etiology may drastically influence subsequent development of CST pathways. Here we describe the pathophysiology underlying impaired upper extremity function, with particular emphasis on the relation between CST damage and hand function. We also describe the resulting sensory and motor deficits, with an emphasis on studies of precision grip, which highlight impairments in motor execution, sensorimotor integration, motor planning, and bimanual coordination beyond dexterity impairments. We show that the type and extent of early brain damage and/or CST reorganization is highly predictive of the severity of these impairments. We discuss the clinical implications of these findings, including the intriguing possibility that the specific pathophysiology is predictive of treatment outcomes. We suggest that a 'one-treatment fits all approach' may be insufficient, and that future rehabilitation efforts will be best guided by closely relating treatment efficacy with the specific pathophysiology. © 2013 Mac Keith Press.


Stunnenberg H.G.,Radboud University Nijmegen | Vermeulen M.,University Utrecht
BioEssays | Year: 2011

High-throughput genomic sequencing and quantitative mass spectrometry (MS)-based proteomics technology have recently emerged as powerful tools, increasing our understanding of chromatin structure and function. Both of these approaches require substantial investments and expertise in terms of instrumentation, experimental methodology, bioinformatics, and data interpretation and are, therefore, usually applied independently from each other by dedicated research groups. However, when applied reiteratively in the context of epigenetics research these approaches are strongly synergistic in nature. © 2011 WILEY Periodicals, Inc..


Soehardi A.,Radboud University Nijmegen
The International journal of oral & maxillofacial implants | Year: 2011

The present study provides an inventory of the number of fractures that occurred in conjunction with implant placement in edentulous patients in the Dutch population from 1980 to 2007 and estimates the incidence with which this might occur. The study also sought to define the factors that increase the risk of fracture. Questionnaires were sent to all 198 oral and maxillofacial surgeons working in 56 hospitals in the Netherlands. Questions were asked regarding the causes of fractures, the height of the edentulous mandible, and the methods of fracture treatment. Responses were received from 53 of the 56 departments. During the study period, 157 edentulous mandibles fractured in conjunction with implant treatment. All fractures occurred in mandibles with less than 10 mm of height, as measured in the symphysis. An incidence of less than 0.05% was estimated based on an estimated number of 475,000 patients treated with at least two implants during this time to support an overdenture. Reasons for early implant failures were insufficient bone volume, iatrogenic causes, nonintegration, and a narrow arch. Peri-implantitis, trauma, and explantation were associated with fractures occurring 1 year or more after implant placement. Several methods were employed to treat the fractured mandibles, including closed reduction, rigid fixation using osteosynthesis plates, and bone grafts with fixation. In 52% of patients, fracture healing was uneventful; however, in 48% of patients, complications were encountered, including osteomyelitis, nonunion, plate fracture, screw loosening, and dehiscences with subsequent infections. Mandibles with a height of 10 mm or less, as measured at the symphysis, are at risk of fractures and associated complications. The provision of proper informed consent regarding the advantages and disadvantages of placing implants in thin mandibles is essential.


Kording E.,Radboud University Nijmegen
Space Science Reviews | Year: 2014

Accretion is a ubiquitous phenomenon—it is seen in sources ranging from young stars to accreting supermassive black holes in the centres of galaxies. Here, we present the known empirical connections between stellar mass X-ray binaries and active galactic nuclei. We argue that this implies that both the accretion disc and the jet are scale invariant with respect to the black hole mass. Finally, we show that also accretion discs and jets in sources with a different accretor can be connected empirically to accreting black holes, hinting towards a common mechanism of accretion in all sources. © 2014, Springer Science+Business Media Dordrecht.


Kirkpatrick J.P.,Duke University | van der Kogel A.J.,Radboud University Nijmegen | Schultheiss T.E.,City of Hope Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2010

Dose-volume data for myelopathy in humans treated with radiotherapy (RT) to the spine is reviewed, along with pertinent preclinical data. Using conventional fractionation of 1.8-2 Gy/fraction to the full-thickness cord, the estimated risk of myelopathy is <1% and <10% at 54 Gy and 61 Gy, respectively, with a calculated strong dependence on dose/fraction (α/β = 0.87 Gy.) Reirradiation data in animals and humans suggest partial repair of RT-induced subclinical damage becoming evident about 6 months post-RT and increasing over the next 2 years. Reports of myelopathy from stereotactic radiosurgery to spinal lesions appear rare (<1%) when the maximum spinal cord dose is limited to the equivalent of 13 Gy in a single fraction or 20 Gy in three fractions. However, long-term data are insufficient to calculate a dose-volume relationship for myelopathy when the partial cord is treated with a hypofractionated regimen. © 2010 Elsevier Inc. All rights reserved.


Wilder-Smith O.H.G.,Radboud University Nijmegen
Journal of Pain and Palliative Care Pharmacotherapy | Year: 2011

Chronic pain is increasingly recognized as an undesirable outcome after surgery. Predicting risk of postoperative chronic pain, as well as chronic pain prevention or treatment, requires understanding of the processes underlying its development. Quantitative sensory testing research over the last decade has made it possible to start understanding the alterations in central pain processing associated with chronic pain and its development. Chronic pain syndromes are typically characterized by a pronociceptive state of pain processing, e.g., generalized hyperalgesia as a sign of supraspinal central sensitization and poor inhibitory or even facilitatory descending modulation. In the perioperative context, development and progression of chronic pain are accompanied by signs congruent with a shift towards a pronociceptive state. Preoperatively, hyperalgesia and poor descending inhibitory modulation appear to increase the risk of subsequent chronic pain. Postoperatively, abnormal persistence and spread of hyperalgesia, compatible with rostral neuraxial spread of central sensitization, are increasingly linked to the development and progression of chronic pain. These findings, which need further confirmation, suggest that perioperative quantitative sensory testing of pain sensitivity and pain modulation has the potential to become a valuable clinical tool for assessing risk of chronic pain development and for managing its prevention and treatment. © 2011 Informa Healthcare USA, Inc.


De Wijn A.S.,University of Stockholm | De Wijn A.S.,Radboud University Nijmegen
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

The scaling of friction with the contact size A and (in)commensurabilty of nanoscopic and mesoscopic crystals on a regular substrate are investigated analytically for triangular nanocrystals on hexagonal substrates. The crystals are assumed to be stiff, but not completely rigid. Commensurate and incommensurate configurations are identified systematically. It is shown that three distinct friction branches coexist, an incommensurate one that does not scale with the contact size (A0) and two commensurate ones which scale differently (with A1 /2 and A) and are associated with various combinations of commensurate and incommensurate lattice parameters and orientations. This coexistence is a direct consequence of the two-dimensional nature of the contact layer, and such multiplicity exists in all geometries consisting of regular lattices. To demonstrate this, the procedure is repeated for rectangular geometry. The scaling of irregularly shaped crystals is also considered, and again three branches are found (A1 /4,A3 /4,A). Based on the scaling properties, a quantity is defined which can be used to classify commensurability in infinite as well as finite contacts. Finally, the consequences for friction experiments on gold nanocrystals on graphite are discussed. © 2012 American Physical Society.


We investigate the diffusion of cosmic rays into molecular cloud complexes. Using the cosmic-ray diffusion formalism of Protheroe et al., we examine how cosmic rays diffuse into clouds exhibiting different density structures, including a smoothed step-function, as well as Gaussian and inverse-r density distributions, which are well known to trace the structure of star-forming regions. These density distributions were modeled as an approximation to the Galactic center cloud G0.216+0.016, a recently discovered massive dust clump that exhibits limited signs of massive star formation and thus may be the best region in the Galaxy to observe synchrotron emission from secondary electrons and positrons. Examination of the resulting synchrotron emission, produced by the interaction of cosmic-ray protons interacting with ambient molecular matter producing secondary electrons and positrons reveals that, due to projection effects, limb-brightened morphology results in all cases. However, we find that the Gaussian and inverse-r density distributions show much broader flux density distributions than step-function distributions. Significantly, some of the compact (compared to the 2.″2 resolution, 5.3 GHz Karl G. Jansky Very Large Array (JVLA) observations) sources show non-thermal emission, which may potentially be explained by the density structure and the lack of diffusion of cosmic rays into the cloud. We find that we can match the 5.3 and 20 GHz flux densities of the non-thermal source JVLA 1 and 6 from Rodríguez & Zapata with a local cosmic-ray flux density, a diffusion coefficient suppression factor of χ = 0.1-0.01 for a coefficient of 3 × 1027 cm-2 s-1, and a magnetic field strength of 470 μG. © 2014. The American Astronomical Society. All rights reserved..


Muradian R.,Radboud University Nijmegen | Rival L.,University of Oxford
Ecosystem Services | Year: 2012

The spread of the ecosystem services framework has been accompanied by the promotion of market-based policy instruments for environmental governance. In this paper we clarify the rationale, policy goals and governance challenges of the ecosystem services framework. After systematizing the limitations of market-based policy tools for enhancing the provision of ecosystem services, we argue that hybrid regimes are more suitable (compared to pure markets or hierarchies) to deal with the governance challenges derived from the characteristics of ecosystem services, particularly their common good character and their intrinsic complexity. The paper pleads for an alternative conceptual underpinning of market-based instruments, in order to make them more compatible with hybrid forms of governance. We discuss the major implications of such analytical shift. © 2012.


de Boode W.-P.,Radboud University Nijmegen
Early Human Development | Year: 2010

There is an increased interest in methods of objective cardiac output measurement in critically ill patients. Several techniques are available for measurement of cardiac output in children, although this remains very complex in newborns. Cardiac output monitoring could provide essential information to guide hemodynamic management. An overview is given of various methods of cardiac output monitoring with advantages and major limitations of each technology together with a short explanation of the basic principles. © 2010 Elsevier Ltd.


McCollam A.,Radboud University Nijmegen
Review of Scientific Instruments | Year: 2011

We describe how the full, isotropic and anisotropic, magnetisation of samples as small as tens of micrometers in size can be sensitively measured using a piezoresistive microcantilever and a small, moveable ferromagnet. Depending on the position of the ferromagnet, a strong but highly local field gradient of up to ∼4200 T/m can be applied at the sample or removed completely during a single measurement. In this way, the magnetic force and torque on the sample can be independently determined without moving the sample or cycling the experimental system. The technique can be used from millikelvin temperatures to ∼85 K and in magnetic fields from 2 T to the highest fields available. We demonstrate its application in measurements of the semimagnetic semiconductor Hg1 - xFexSe, where we achieved a moment sensitivity of better than 2.5 10-14 J/T for both isotropic and anisotropic components. © 2011 American Institute of Physics.


Liem K.D.,Radboud University Nijmegen | Greisen G.,Rigshospitalet
Early Human Development | Year: 2010

The most important cerebrovascular injuries in newborn infants, particularly in preterm infants, are cerebral haemorrhage and ischemic injury. The typical cerebral vascular anatomy and the disturbance of cerebral haemodynamics play important roles in the pathophysiology. The term 'cerebral haemodynamics' includes cerebral blood flow (CBF), cerebral blood flow velocity, and cerebral blood volume (CBV). Therapy aimed at changing vascular anatomy is not available. Therefore, prevention of disturbances in CBF and CBV is pivotal. However, continuous monitoring of CBF and CBV is still unavailable for clinical use. Tissue oxygenation may be used as a surrogate for CBF, although precision is still questionable. General knowledge of the regulation of CBF and CBV is important. Although this knowledge is still incomplete, especially regarding autoregulation and the exact role of CBV, it is still useful. Using it even without knowing the exact level of CBF and CBV, it is possible to aim to keep CBF and CBV stable. Future research should focus on development of monitoring tools, gaining more insight in neonatal cerebral autoregulation, and demonstrating clinical benefits of a 'cerebral perfusion-oriented' therapy. © 2010 Elsevier Ltd.


Dijkstra S.,Radboud University Nijmegen
Clinical biochemistry | Year: 2014

In the era of upcoming techniques for molecular profiling, breakthroughs led to new discoveries in the field of prostate cancer (PCa) biomarkers. Since the early 1990s a tremendous increase in PCa incidence is seen, dedicated to the introduction of prostate specific antigen (PSA) testing. However, due to its lack of specificity many men undergo unnecessary biopsies, resulting in a rising incidence of clinically insignificant PCa. To overcome this drawback, cancer specific biomarkers are needed to identify patients who are at high risk of harbouring PCa and to distinguish patients with aggressive disease from patients with insignificant cancer. The most non-invasive, easy to obtain substrate for biomarker measurement is urine. The most promising markers to date are PCA3 and TMPRSS2-ERG. Both markers demonstrate to have a higher specificity and diagnostic accuracy for PCa outcome compared to serum PSA. This might better predict the presence of PCa and therefore reduce the number of unnecessary biopsies. Combining both markers in a panel might result in an even higher diagnostic accuracy, given the heterogeneity of the disease. In PCa management, circulating tumour cells (CTCs) detected in the blood seem a promising tool to predict treatment response and survival benefit. Although results appear to be encouraging, the biggest challenge about new markers in PCa is to validate them in large clinical trials and subsequently implement these markers into clinical practice. In this review we discuss the clinical usefulness of novel, non-invasive tests in PCa management. © 2013.


Jacquemyn H.,Catholic University of Leuven | Brys R.,Research Institute for Nature and Forest | Jongejans E.,Radboud University Nijmegen
Journal of Ecology | Year: 2010

1. In woodland herbs, the probability of flowering and costs associated with reproduction may strongly depend on environmental context (shade vs. light habitats) and on plant size. This may be particularly true for tuberous orchids that inhabit woodlands, as the amount of incoming radiation and total leaf area strongly determine photosynthetic capacity and hence the amount of carbohydrates that can be relocated to below-ground storage organs that form next year's rosette and flowering stalk. 2. To fully comprehend the impact of size-dependent reproduction on population dynamics under varying light conditions, life cycle models should therefore include plant size in a continuous manner. In this study, annual changes in plant size and demographic behaviour of the tuberous perennial orchid Orchis purpurea were monitored during seven consecutive years (2003-2009) in open and shaded woodland. Integral projection models (IPMs) and life table response experiments (LTRE) were used to investigate the extent to which variation in plant size affected the overall population dynamics of this species and to decompose differences in population growth rates between populations of open and shaded woodland into contributions from growth, survival and reproduction. 3. Both plants in shaded and light environments needed to be a certain size to initiate flowering, but this threshold size was almost three times as large in shaded environments as in light environments. Plants in open woodlands flowered more frequently over the years, showed less size regression after flowering and produced significantly more fruits than plants in shaded environments, resulting in significantly larger population growth rates. 4. Our life cycle models revealed that costs of reproduction, measured at the population-level, were small in the light environment, and more than buffered by the increase in survival of flowering plants compared to non-flowering plants. In the shade environment, however, the costs of reproduction were significant and made the difference between a stable (current) and a growing (without reproduction costs) population. 5. Synthesis. Light penetration to the soil is a key variable determining population dynamics of woodland orchids. Our analyses show that differences in vital rates related to size-dependent reproduction (flowering) and growth are essential drivers of changes in orchid population dynamics in different light environments. The combination of IPMs and LTREs thus proves to be very useful when studying the fitness consequences of size- and context-dependent phenomena like flowering strategies and costs of reproduction. © 2010 The Authors. Journal compilation © 2010 British Ecological Society.


Beulen L.,Radboud University Nijmegen
European Journal of Human Genetics | Year: 2016

Early in pregnancy women and their partners face the complex decision on whether or not to participate in prenatal testing for fetal chromosomal abnormalities. Several studies show that the majority of pregnant women currently do not make informed decisions regarding prenatal testing. As the range of prenatal tests is expanding due to the development of new techniques such as non-invasive prenatal testing (NIPT), autonomous reproductive decision-making is increasingly challenging. In this study, a randomised controlled trial was conducted to evaluate the effect of a web-based multimedia decision aid on decision-making regarding prenatal testing. The decision aid provided both written and audiovisual information on prenatal tests currently available, that is, prenatal screening by first-trimester combined testing, NIPT and invasive diagnostic testing through chorionic villus sampling or amniocentesis. Furthermore, it contained values clarification exercises encouraging pregnant women to reflect on the potential harms and benefits of having prenatal tests performed. The use of the decision aid improved informed decision-making regarding prenatal testing. Of pregnant women allocated to the intervention group (n=130) 82.3% made an informed choice compared with 66.4% of women in the control group (n=131), P=0.004. As the vast majority of pregnant women made decisions consistent with their attitudes towards having prenatal testing performed, this improvement in informed decision-making could be attributed mainly to an increase in decision-relevant knowledge. This study shows that the implementation of a web-based multimedia decision aid directly facilitates the ultimate goal of prenatal testing for fetal chromosomal abnormalities, which is enabling informed autonomous reproductive choice.European Journal of Human Genetics advance online publication, 18 May 2016; doi:10.1038/ejhg.2016.39. © 2016 Macmillan Publishers Limited


Tjalsma H.,Radboud University Nijmegen
Expert Review of Proteomics | Year: 2010

The early detection of colorectal cancer is one of the great challenges in the battle against this disease. However, owing to its heterogeneous character, single markers are not likely to provide sufficient diagnostic power to be used in colorectal cancer population screens. This review provides an overview of recent studies aimed at the discovery of new diagnostic protein markers through proteomics-based approaches. It indicates that studies that start with the proteomic analysis of tumor tissue or tumor cell lines (near the source) have a high potential to yield novel and colorectal cancer-specific biomarkers. In the next step, the diagnostic accuracy of these candidate markers can be assessed by a targeted ELISA assay using serum from colorectal cancer patients and healthy controls. Instead, direct proteomic analysis of serum yields predominantly secondary markers composed of fragments of abundant serum proteins that may be associated with tumor-associated protease activity, and alternatively, immunoproteomic analysis of the serum antibody repertoire provides a valuable tool to identify the molecular imprint of colorectal cancer-associated antigens directly from patient serum samples. The latter approach also allows a relatively easy translation into targeted assays. Eventually, multimarker assays should be developed to reach a diagnostic accuracy that meets the stringent criteria for colorectal cancer screening at the population level. © 2010 Expert Reviews Ltd.


Larsson S.,Uppsala University | Hannink G.,Radboud University Nijmegen
Injury | Year: 2011

More than a decade has passed since the first injectable bone substitutes were introduced for use in orthopaedic trauma, and over recent years the number of commercial products has increased dramatically. Despite the fact that these bone substitutes have been on the market for many years, knowledge amongst potential users on how and when they might be useful is still fairly limited. Most injectable bone substitutes belong to one of two major groups: by far the largest group contains products based on various calcium phosphate (CP) mixtures, whilst the smaller group consists of calcium sulphate (CS) compounds. Following mixing, the CP or CS paste can be injected into - for instance - a fracture space for augmentation as an alternative to bone graft, or around a screw for augmentation if the bone is weak. Within minutes an in situ process makes the substitute hard; the mechanical strength in compression resembles that of cancellous bone, whereas the strength in bending and shear is lower. Over time, CP products undergo remodelling through a cell-mediated process that seems to mimic the normal bone remodelling, whilst CS products are dissolved through a faster process that is not cell-mediated. For CP, a number of clinical studies have shown that it can be useful for augmentation of metaphyseal fractures when a space is present. Randomised studies have verified that CP works especially well in tibial plateau fractures when compared with conventional bone grafting. So far the number of clinical studies on CS products is very low. Development at present seems to be heading towards premixed or directly mixed products as well as new compounds that contain fibres or other components to enhance bending and shear strength. Products that are based on combinations of CP and CS are also being developed to combine the fast-dissolving CS with the stronger and more slowly remodelling CP. Injectable bone substitutes, and especially CS, have also been targeted as potentially good carriers for antibiotics and growth factors. © 2011 Published by Elsevier Ltd.


Donnelly J.P.,Radboud University Nijmegen | Lahav M.,Tel Aviv University
Journal of Antimicrobial Chemotherapy | Year: 2012

Mucormycosis can be devastating and, as yet, there are no ideal therapies available. Observations that iron chelation may be a useful adjunct to antifungal treatment encouraged Spellberg et al. (J Antimicrob Chemother 2012; 715-22) to undertake a trial of deferasirox combined with liposomal amphotericin B (AmBisome®) as short-term therapy for mucormycosis. The results were disappointing as patients treated with deferasirox had a higher mortality rate at 90 days, leading the authors to conclude that the data did not support a role for initial, adjunctive deferasirox therapy for mucormycosis. We review the issues arising from this study to help decide whether the evidence that now exists supports further studies or represents the end of this line of enquiry. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Maris E.,Radboud University Nijmegen
Psychophysiology | Year: 2012

This article describes the mechanics and rationale of four different approaches to the statistical testing of electrophysiological data: (1) the Neyman-Pearson approach, (2) the permutation-based approach, (3), the bootstrap-based approach, and (4) the Bayesian approach. These approaches are evaluated from the perspective of electrophysiological studies, which involve multivariate (i.e., spatiotemporal) observations in which source-level signals are picked up to a certain extent by all sensors. Besides formal statistical techniques, there are also techniques that do not involve probability calculations but are very useful in dealing with multivariate data (i.e., verification of data-based predictions, cross-validation, and localizers). Moreover, data-based decision making can also be informed by mechanistic evidence that is provided by the structure in the data. © 2011 Society for Psychophysiological Research.


Viergever R.F.,Radboud University Nijmegen | Terry R.F.,World Health Organization | Karam G.,World Health Organization
Bulletin of the World Health Organization | Year: 2013

Objective To explore what can be learnt about the current composition of the "global landscape" of health research and development (R&D) from data on the World Health Organization's International Clinical Trials Registry Platform (ICTRP). Methods A random 5% sample of the records of clinical trials that were registered as interventional and actively recruiting was taken from the ICTRP database. Findings Overall, 2381 records of trials were investigated. Analysis of these records indicated that, for every million disability-adjusted life years (DALYs) caused by communicable, maternal, perinatal and nutritional conditions, by noncommunicable diseases, or by injuries, the ICTRP database contained an estimated 7.4, 52.4 and 6.0 trials in which these causes of burden of disease were being investigated, respectively. For every million DALYs in high-income, upper-middle-income, lower-middle-income and low-income countries, an estimated 292.7, 13.4, 3.0 and 0.8 registered trials, respectively, were recruiting in such countries. Conclusion The ICTRP constitutes a valuable resource for assessing the global distribution of clinical trials and for informing policy development for health R&D. Populations in lower-income countries receive much less attention, in terms of clinical trial research, than populations in higher-income countries.


Janner A.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2010

The differentiation of the human rhinovirus into serotypes, all having very similar structures and the same architecture, is shown to be related to the packing of the viruses in the crystal and to its space-group symmetry. The molecular crystallographic properties (here described in terms of a molecular lattice M instead of the form lattice F considered in previous publications) appear to be compatible with the crystal structure and with the packing lattice P, introduced in Part I [Janner (2010). Acta Cryst. A66, 301-311]. On the basis of the enclosing forms of the capsid, a sphere packing is considered, where the spheres touch at kissing points. Residues of each of the four coat proteins (VP1, VP2, VP3, VP4), having a minimal distance from the kissing points, define a set of kissing point related (KPR) residues. In this set only four different residues occur, one for each coat protein, ordered into symmetric clusters {already classified in a previous publication [Janner (2006). Acta Cryst. A62, 270-286]} and indexed by neighbouring lattice points of P (or equivalently of M). The indexed KPR residues allow a fingerprint characterization of the five rhinovirus serotypes whose structures are known (HRV16, HRV14, HRV3, HRV2 and HRV1A). In the fingerprint they occur as internal (if inside the given capsid), as external (if belonging to the neighbouring viruses) or as a contact residue (if at a kissing point position). The same fingerprint, periodically extended, permits a coarse-grained reconstruction of the essential properties of the crystal packing, invariant with respect to the space group of the serotype. © 2010 International Union of Crystallography. Printed in Singapore-all rights reserved.


de Vries M.,Radboud University Nijmegen
Andrology | Year: 2013

During the last phase of spermatogenesis, called spermiogenesis, the nucleosome-based chromatin structure is replaced by a protamine-based DNA packaging. Not much is known about the chromatin remodelling involved in humans and animals. Here, we have investigated initiation of chromatin remodelling over seven probands of which five were diagnosed with non-obstructive azoospermia (NOA) and two with obstructive azoospermia (OA) (failed vaso-vasostomy patients with proven fertility prior to vasectomy, Johnsen scores ≥9). Chromatin remodelling was studied evaluating the presence of nucleosomes, histone H3, pre-protamine 2 and protamine 1. This approach was feasible since the local initiation of nucleosome eviction in the sub acrosomal domain, which was visible in alkaline nuclear spread preparations. The patterns of nucleosome and H3 loss were largely congruent. Nucleus wide incorporation of protamine 1 could already be observed at the late round spermatid stage. Both for nucleosome loss and for protamine 1 incorporation, there was distinct variation within and between probands. This did not relate to the efficiency of sperm production per meiocyte. Pre-protamine 2 was always confined to the subacrosomal domain, confirming the role of this area in chromatin remodelling. © 2013 American Society of Andrology and European Academy of Andrology.


Nagtegaal I.D.,Radboud University Nijmegen | Duffy S.W.,Wolfson Institute of Preventive Medicine
Breast Cancer Research and Treatment | Year: 2013

Population screening has brought about changes in both the incidence and mortality rates of patients with breast cancer. Large numbers of small screen-detected tumors have inspired discussions about overdiagnosis based on potential biological differences between screen-detected and symptomatic cancers. In the current systematic review, we analyzed the relation and the interaction of tumor size and nodal status in correlation with screening. Smaller tumors were more frequently screen detected (pT1 78.5 %) than symptomatic (pT1 61.7 %, p < 0.001), with a RR of 1.6 (95 % CI 1.4-1.8, n = 41,209). In the screened population, pT1 tumors were also more frequent (68.5 vs 49.9 %, n = 51,171, p < 0.001). Positive lymph nodes were less frequent in screen-detected tumors (26.8 vs 46.3 %, n = 43,705, p < 0.001) as well as in screened populations as a whole (24.1 vs 44.9 %, n = 49,581, p < 0.001). The relation between size and nodal status was not different between the screen-detected and the symptomatic tumors [pT2+N+ OR 2.42 (95 % CI 1.69-3.48) vs OR 2.91 (95 % CI 2.41-3.51)], suggesting that biological differences, if present, are small. In this systematic review, we confirmed both the association of screening with smaller tumor size at presentation and the consequent reduction in lymph node metastases. © 2012 Springer Science+Business Media New York.


Falcke H.,Radboud University Nijmegen | Falcke H.,Max Planck Institute for Radio Astronomy | Rezzolla L.,Max Planck Institute For Gravitationsphysik | Rezzolla L.,Institute For Theoretische Physik
Astronomy and Astrophysics | Year: 2014

Context. Several fast radio bursts have been discovered recently, showing a bright, highly dispersed millisecond radio pulse. The pulses do not repeat and are not associated with a known pulsar or gamma-ray burst. The high dispersion suggests sources at cosmological distances, hence implying an extremely high radio luminosity, far larger than the power of single pulses from a pulsar. Aims. We suggest that a fast radio burst represents the final signal of a supramassive rotating neutron star that collapses to a black hole due to magnetic braking. The neutron star is initially above the critical mass for non-rotating models and is supported by rapid rotation. As magnetic braking constantly reduces the spin, the neutron star will suddenly collapse to a black hole several thousand to million years after its birth. Methods. We discuss several formation scenarios for supramassive neutron stars and estimate the possible observational signatures making use of the results of recent numerical general-relativistic calculations. Results. While the collapse will hide the stellar surface behind an event horizon, the magnetic-field lines will snap violently. This can turn an almost ordinary pulsar into a bright radio "blitzar": accelerated electrons from the travelling magnetic shock dissipate a significant fraction of the magnetosphere and produce a massive radio burst that is observable out to z > 0.7. Only a few per cent of the neutron stars need to be supramassive in order to explain the observed rate. Conclusions. We suggest the intriguing possibility that fast radio bursts might trace the solitary and almost silent formation of stellar mass black holes at high redshifts. These bursts could be an electromagnetic complement to gravitational-wave emission and reveal a new formation and evolutionary channel for black holes and neutron stars that are not seen as gamma-ray bursts. If supramassive neutron stars are formed at birth and not by accretion, radio observations of these bursts could trace the core-collapse supernova rate throughout the universe. © 2014 ESO.


Meesters J.A.,Radboud University Nijmegen
Integrated environmental assessment and management | Year: 2013

Engineered nanomaterials (ENMs) possess novel properties making them attractive for application in a wide spectrum of fields. These novel properties are not accounted for in the environmental risk assessment methods that the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) proposes in their guidance on environmental exposure estimation, although ENMs are already applied in a variety of consumer and industrial products. It is thus necessary to evaluate the guidance document REACH provides on environmental exposure estimation on its applicability to ENMs. This is most urgently the case for engineered nanoparticles (ENPs), as the novel properties are most often only applicable to them. The environmental fate of ENPs was reviewed and compared to the environmental fate of chemicals according to the REACH guidance. Major deviations between the fate of ENPs and predicted fate by REACH were found. They were related to at least 1 of 3 major assumptions made in REACH guidance: 1) in REACH, environmental alteration processes are all thought of as removal processes, whereas alterations of ENPs in the environment may greatly affect their properties, environmental effects, and behavior, 2) in REACH, chemicals are supposed to dissolve instantaneously and completely on release into the environment, whereas ENPs should be treated as nondissolved nanosized solids, and 3) in REACH, partitioning of dissolved chemicals to solid particles in air, water, and soil is estimated with thermodynamic equilibrium coefficients, but in the case of ENPs thermodynamic equilibrium between "dispersed" and "attached" states is generally not expected. The environmental exposure assessment of REACH therefore needs adjustment to cover the specific environmental fate of ENPs. Incorporation of the specific environmental fate processes of ENPs into the environmental risk assessment framework of REACH requires a pragmatic approach. Copyright © 2013 SETAC.


Guinea F.,CSIC - Institute of Materials Science | Geim A.K.,University of Manchester | Katsnelson M.I.,Radboud University Nijmegen | Novoselov K.S.,University of Manchester
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

We analyze the mechanical deformations that are required to create uniform pseudomagnetic fields in graphene. It is shown that, if a ribbon is bent in-plane into a circular arc, this can lead to fields exceeding 10 T, which is sufficient for the observation of pseudo-Landau quantization. The arc geometry is simpler than those suggested previously and, in our opinion, has much better chances to be realized experimentally soon. The effects of a scalar potential induced by dilatation in this geometry is shown to be negligible. © 2010 The American Physical Society.


Nijhof S.L.,University Utrecht | Bleijenberg G.,Radboud University Nijmegen | Uiterwaal C.S.P.M.,University Utrecht | Kimpen J.L.L.,University Utrecht | Van De Putte E.M.,University Utrecht
The Lancet | Year: 2012

Background: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care. Methods: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666. Findings: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months - full school attendance (50 [75] vs 10 [16], relative risk 4·8, 95 CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85] vs 17 [27], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78] vs 13 [20], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported. Interpretation: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale. Funding: Netherlands Organisation for Health Research and Development. © 2012 Elsevier Ltd.


Van Ingen J.,Radboud University Nijmegen
Seminars in Respiratory and Critical Care Medicine | Year: 2013

The nontuberculous mycobacteria (NTM) are typically environmental organisms residing in soil and water. Although generally of low pathogenicity to humans, NTM can cause a wide array of clinical diseases; pulmonary disease is most frequent, followed by lymphadenitis in children, skin disease by M. marinum (particularly in fish tank fanciers), and other extrapulmonary or disseminated infections in severely immunocompromised patients. Of the >140 NTM species reported in the literature, 25 species have been strongly associated with NTM diseases; the remainder are environmental organisms rarely encountered in clinical samples. Correct species identification is very important because NTM species differ in their clinical relevance. Further, NTM differ strongly in their growth rate, temperature tolerance, and drug susceptibility. The diagnosis of NTM disease is complex and requires good communication between clinicians, radiologists, and microbiologists. Isolation of M. kansasii and (in northwestern Europe) M. malmoense from pulmonary specimens usually indicates disease, whereas Mycobacterium gordonae and, to a lesser extent, M. simiae or M. chelonae are typically contaminants rather than causative agents of true disease. Mycobacterium avium complex (MAC), M. xenopi, and M. abscessus form an intermediate category between these two extremes. This review covers the clinical and laboratory diagnosis of NTM diseases and particularities for the different disease types and patient populations. Because of limited sensitivity and specificity of symptoms, radiology, and direct microscopy of clinical samples, culture remains the gold standard. Yet culture is time consuming and demands the use of multiple media types and incubation temperatures to optimize the yield. Outside of reference centers, such elaborate culture algorithms are scarce. © 2013 by Thieme Medical Publishers, Inc.


Koenders P.G.,Beter Occupational and Health Services | Van Strien T.,Radboud University Nijmegen
Journal of Occupational and Environmental Medicine | Year: 2011

Objective: To examine the associations between the lifestyle factors-sports, alcohol, nutrition, overweight, and smoking, the eating styles of dietary restraint, external eating, and emotional eating on the one hand, and the change in body mass index (BMI) on the other hand. METHODS: Using a Web-based lifestyle questionnaire, responses were obtained from 1562 employees. RESULTS: We found a consistent main effect of emotional eating and doing sports on change in BMI. High emotional eating was related to weight gain, whereas a high level of sporting was related to weight loss. Restrained eating and external eating were not found to have a significant influence on change in BMI. Additionally, a consistent moderator effect of sporting on emotional eating was found (P < .05). The association between BMI change and emotional eating was less strong for employees with high engagement in strenuous sports compared with those with low engagement in strenuous sports. This indicates that strenuous physical activity can indeed attenuate the positive association between emotional eating and body weight gain. CONCLUSION: Emotions may drive people with overweight and obesity to overeat. Sports activities may attenuate but do not solve the problem. If we want to cure the disease, psychological treatment strategies have to be developed. Copyright © 2011 by American College of Occupational and Environmental Medicine.


Attreed M.,Yeshiva University | Desbois M.,Yeshiva University | Van Kuppevelt T.H.,Radboud University Nijmegen | Bulow H.E.,Yeshiva University
Nature Methods | Year: 2012

Modification patterns of heparan sulfate coordinate protein function in metazoans, yet in vivo imaging of such non-genetically encoded structures has been impossible. Here we report a transgenic method in Caenorhabditis elegans that allows direct live imaging of specific heparan sulfate modification patterns. This experimental approach reveals a dynamic and cell-specific heparan sulfate landscape and could in principle be adapted to visualize and analyze any extracellular molecule in vivo. © 2012 Nature America, Inc. All rights reserved.


Ouborg N.J.,Radboud University Nijmegen
Biology Letters | Year: 2010

As one of the final activities of the ESF-CONGEN Networking programme, a conference entitled 'Integrating Population Genetics and Conservation Biology' was held at Trondheim, Norway, from 23 to 26 May 2009. Conference speakers and poster presenters gave a display of the state-of-the-art developments in the field of conservation genetics. Over the five-year running period of the successful ESF-CONGEN Networking programme, much progress has been made in theoretical approaches, basic research on inbreeding depression and other genetic processes associated with habitat fragmentation and conservation issues, and with applying principles of conservation genetics in the conservation of many species. Future perspectives were also discussed in the conference, and it was concluded that conservation genetics is evolving into conservation genomics, while at the same time basic and applied research on threatened species and populations from a population genetic point of view continues to be emphasized. © 2009 The Royal Society.


Van Eck C.L.,Radboud University Nijmegen | Brown J.C.,University of Calgary | Shukurov A.,Northumbria University | Fletcher A.,Northumbria University
Astrophysical Journal | Year: 2015

Both observations and modeling of magnetic fields in the diffuse interstellar gas of spiral galaxies are well developed, but the theory has been confronted with observations for only a handful of individual galaxies. There is now sufficient data to consider the statistical properties of galactic magnetic fields. We have collected data from the literature on the magnetic fields and interstellar media of 20 spiral galaxies, and tested for various physically motivated correlations between magnetic field and interstellar medium parameters. Clear correlations emerge between the total magnetic field strength and molecular gas density as well as the star formation rate. The magnetic pitch angle exhibits correlations with the total gas density, the star formation rate, and the strength of the axisymmetric component of the mean magnetic field. The total and mean magnetic field strengths exhibit a noticeable degree of correlation, suggesting a universal behavior of the degree of order in galactic magnetic fields. We also compare the predictions of galactic dynamo theory to observed magnetic field parameters and identify directions in which theory and observations might be usefully developed. © 2015. The American Astronomical Society. All rights reserved.


Hagenaars M.A.,Health and Neuropsychology | van Minnen A.,GGZ Nijmegen | Hoogduin K.A.L.,Radboud University Nijmegen
Behaviour Research and Therapy | Year: 2010

This study investigates the impact of dissociative phenomena and depression on the efficacy of prolonged exposure treatment in 71 patients with posttraumatic stress disorder (PTSD). Diagnoses, comorbidity, pretreatment depressive symptoms, PTSD symptom severity, and dissociative phenomena (trait dissociation, numbing, and depersonalization) were assessed at pretreatment using semi-structured interviews and questionnaires. In a pretreatment behavioral exposure test, patients were imaginally exposed to (part of) their trauma memory for 9 min, during which subjective fear was assessed. At posttreatment and 6 months follow-up PTSD, depressive and dissociative symptoms were again assessed in the completers (n = 60). Pretreatment levels of dissociative and depressive symptoms were similar in dropouts and completers and none of the dissociative phenomena nor depression predicted improvement. Against expectations, dissociative phenomena and depression were associated with enhanced rather than impeded fear activation during the behavioral exposure test. However, these effects disappeared after controlling for initial PTSD severity. Hence, rather than supporting contraindication, the current results imply that patients presenting with even severe dissociative or depressive symptoms may profit similarly from exposure treatment as do patients with minimal dissociative or depressive symptoms. © 2009 Elsevier Ltd. All rights reserved.


Metcalf C.J.E.,University of Oxford | McMahon S.M.,Smithsonian Environmental Research Center | Salguero-Gomez R.,Max Planck Institute for Demographic Research | Jongejans E.,Radboud University Nijmegen
Methods in Ecology and Evolution | Year: 2013

Structured demographic models offer powerful methods for addressing important questions in ecology and evolution. Integral Projection Models (IPMs) are related to classic matrix models, but are more appropriate for modelling structured populations when the variable describing individuals' demography is continuous (e.g. size, weight, etc.). We present IPMpack, a free open-source software (R) package for building IPMs. The package estimates key population characteristics from IPMs, such as population growth rate in both deterministic and stochastic environments, age-specific trajectories of survival and reproduction, and sensitivities and elasticities to changes in underlying vital rates. IPMpack can be used for species across a range of life cycle complexity and can include continuous and discrete (e.g. seed bank, hibernation) state variables, as well as environmental covariates of interest. Methods for diagnostics, sensitivity analyses, plotting, model comparison and many other features allow users to move from data input through analysis to inference using an array of internal functions. IPMpack fills a need for readily usable tools for constructing and analysing IPMs and is designed to facilitate their use for experts and open up their use for those researchers who have little experience in the details of population models. A standardized IPM modelling framework will also facilitate cross-study and cross-species comparative demography, encouraging the exploration of broader ecological and evolutionary questions that can be addressed by population models. © 2012 The Authors. Methods in Ecology and Evolution © 2012 British Ecological Society.


Van Weel C.,Radboud University Nijmegen
Journal of Evaluation in Clinical Practice | Year: 2011

Rationale, aims and objectives: Most professional medical care is provided in the community, and this determines the importance of primary care for the health care system. As family doctors are involved in the care of different health problems over time to the same individual, the personal dimension is strong. This paper analyses the importance of personcentred medicine from the perspective of primary care and family medicine. Methods: The views and opinions of the leadership of the World Organization of Family Doctors, Wonca, provided the background material. Wonca brings together national colleges and academies of family medicine around the world. Results: The community, with its social, cultural and economic characteristics, is an important determinant of illness, health and disease. This shapes the personal relation between patient and family physician, with its basis of trust, and determines the effectiveness with which primary care functions. Continuity and integration of care are important person-centred 'techniques'. Conclusions: As the effectiveness of primary care is a major factor for overall effective health care, it is important to come to a better understanding of how to address the personal context of care and the mechanisms through which this determines outcome of care. © 2011 Blackwell Publishing Ltd.


Friedl P.,Radboud University Nijmegen | Friedl P.,University of Houston | Friedl P.,University of Wurzburg | Alexander S.,University of Houston | Alexander S.,University of Wurzburg
Cell | Year: 2011

Cancer invasion is a cell-and tissue-driven process for which the physical, cellular, and molecular determinants adapt and react throughout the progression of the disease. Cancer invasion is initiated and maintained by signaling pathways that control cytoskeletal dynamics in tumor cells and the turnover of cell-matrix and cell-cell junctions, followed by cell migration into the adjacent tissue. Here, we describe the cell-matrix and cell-cell adhesion, protease, and cytokine systems that underlie tissue invasion by cancer cells. We explain how the reciprocal reprogramming of both the tumor cells and the surrounding tissue structures not only guides invasion, but also generates diverse modes of dissemination. The resulting "plasticity" contributes to the generation of diverse cancer invasion routes and programs, enhanced tumor heterogeneity, and ultimately sustained metastatic dissemination. © 2011 Elsevier Inc.


Voet N.B.,Radboud University Nijmegen
The Cochrane database of systematic reviews | Year: 2013

Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. This is an update of a review first published in 2004. To examine the safety and efficacy of strength training and aerobic exercise training in people with a muscle disease. We searched the Cochrane Neuromuscular Disease Group Specialized Register (July 2012), CENTRAL (2012 Issue 3 of 4), MEDLINE (January 1946 to July 2012), EMBASE (January 1974 to July 2012), EMBASE Classic (1947 to 1973) and CINAHL (January 1982 to July 2012). Randomised or quasi-randomised controlled trials comparing strength training or aerobic exercise programmes, or both, to no training, and lasting at least six weeks, in people with a well-described diagnosis of a muscle disease.We did not use the reporting of specific outcomes as a study selection criterion. Two authors independently assessed trial quality and extracted the data obtained from the full text-articles and from the original investigators. We collected adverse event data from included studies. We included five trials (170 participants). The first trial compared the effect of strength training versus no training in 36 people with myotonic dystrophy. The second trial compared aerobic exercise training versus no training in 14 people with polymyositis and dermatomyositis. The third trial compared strength training versus no training in a factorial trial that also compared albuterol with placebo, in 65 people with facioscapulohumeral muscular dystrophy (FSHD). The fourth trial compared combined strength training and aerobic exercise versus no training in 18 people with mitochondrial myopathy. The fifth trial compared combined strength training and aerobic exercise versus no training in 35 people with myotonic dystrophy type 1.In both myotonic dystrophy trials and the dermatomyositis and polymyositis trial there were no significant differences between training and non-training groups for primary and secondary outcome measures. The risk of bias of the strength training trial in myotonic dystrophy and the aerobic exercise trial in polymyositis and dermatomyositis was judged as uncertain, and for the combined strength training and aerobic exercise trial, the risk of bias was judged as adequate. In the FSHD trial, for which the risk of bias was judged as adequate, a +1.17 kg difference (95% confidence interval (CI) 0.18 to 2.16) in dynamic strength of elbow flexors in favour of the training group reached statistical significance. In the mitochondrial myopathy trial, there were no significant differences in dynamic strength measures between training and non-training groups. Exercise duration and distance cycled in a submaximal endurance test increased significantly in the training group compared to the control group. The differences in mean time and mean distance cycled till exhaustion between groups were 23.70 min (95% CI 2.63 to 44.77) and 9.70 km (95% CI 1.51 to 17.89), respectively. The risk of bias was judged as uncertain. In all trials, no adverse events were reported. Moderate-intensity strength training in myotonic dystrophy and FSHD and aerobic exercise training in dermatomyositis and polymyositis and myotonic dystrophy type I appear to do no harm, but there is insufficient evidence to conclude that they offer benefit. In mitochondrial myopathy, aerobic exercise combined with strength training appears to be safe and may be effective in increasing submaximal endurance capacity. Limitations in the design of studies in other muscle diseases prevent more general conclusions in these disorders.


Rubartelli A.,Italian National Cancer Institute | Gattorno M.,G Gaslini Institute | Netea M.G.,Radboud University Nijmegen | Dinarello C.A.,Aurora University
Trends in Immunology | Year: 2011

Several inflammation-related processes, including inflammasome activation and interleukin (IL)-1β secretion, are dependent on redox signaling. However, the type of redox response involved as well as the relevant role of pro-oxidant and antioxidant events are matters of intense debate. By comparing leukemic myeloid cells, healthy monocytes and macrophages, as well as monocytes from patients carrying mutations in members of the Nod-like receptor (NLR) gene family, we have drawn a model that reconciles previous conflicting hypotheses. We propose that the redox state of resting inflammatory cells determines the type and extent of redox response to pattern recognition receptor stimulation, which in turn dictates the efficiency of inflammasome activation. The impact on genetic and acquired inflammatory diseases will be discussed. © 2011 Elsevier Ltd.


Elmalem E.,University of Cambridge | Kiriy A.,Leibniz Institute of Polymer Research | Huck W.T.S.,University of Cambridge | Huck W.T.S.,Radboud University Nijmegen
Macromolecules | Year: 2011

The first chain-growth Suzuki polymerization of a monomer consisting of two different aromatic groups, to yield a well-defined electron-deficient polymer, poly(9,90-dioctylfluorene-co-benzothiadiazole) (pF8BT), was reported. The polymerization was initiated from 5mol% in THF at 0°C, using 2 M CsF as a base and crown-ether as phase-transfer catalyst. The influence of the end-group on the optical properties of the polymers was studied briefly. The results show that the Pyr-pF8 spectrum is shifted to higher wavelengths in comparison to the spectra of Ph-pF8. The calculated HOMO LUMO energies of pyrene are found to be very close to the reported values for pF8, whereas pF8BT has energetically distant orbitals. In both of the pyrene cap polymers, the pyrene peak at 280 nm can be observed. A control over MW, narrow PDI, and specific end-functions is demonstrated by means of GPC and MALDI-TOF measurements.


Urban J.,Radboud University Nijmegen
CEUR Workshop Proceedings | Year: 2011

This is an attempt at a brief initial overview of the state of the art in the young field of first-order automated reasoning in large theories (ARLT). It is necessarily biased by the author's imperfect knowledge, and hopefully will serve as material provoking further corrections and completions.


Hedayat M.,Tehran University of Medical Sciences | Netea M.G.,Radboud University Nijmegen | Rezaei N.,Tehran University of Medical Sciences | Rezaei N.,University of Sheffield
The Lancet Infectious Diseases | Year: 2011

Toll-like receptors (TLRs) recognise highly conserved molecular structures, collectively known as pathogen-associated molecular patterns. In the past two decades, development and clinical implementation of TLR ligands-ie, chemically modified synthetic derivatives of naturally occurring ligands and fully synthetic small molecules-have been topics of intense research. Targeted manipulation of TLR signalling has been applied clinically to boost vaccine effectiveness, promote a robust T helper 1-predominant immune response against viral infection, or dampen the exaggerated inflammatory response to bacterial infection. Use of these new therapeutic molecules as adjuncts to conventional pharmacotherapy or stand-alone treatments might offer solutions to unmet clinical needs or could replace existing partly effective therapeutic strategies. © 2011 Elsevier Ltd.


Janner A.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2011

Four icosahedral RNA viruses are considered: the cowpea chlorotic mottle virus, the satellite tobacco mosaic virus, the pariacoto virus and the MS2 bacteriophage. The validity of the phenomenological rules derived in previous publications (crystallographic scaling, indexed forms enclosing axial-symmetric clusters, packing lattices of viral crystals) is confirmed and shown to apply equally well to the coat proteins as to the (ordered) RNA chains. © International Union of Crystallography Printed in Singapore - all rights reserved.


Sridhar S.S.,University of Toronto | Freedland S.J.,Duke University | Gleave M.E.,BC Cancer Agency | Higano C.,Seattle Cancer Center Alliance | And 4 more authors.
European Urology | Year: 2014

Context Until recently, the only approved agent for metastatic castration-resistant prostate cancer (mCRPC) was docetaxel chemotherapy. But over the last 5 years, significant advances in the field have led to the approval of five new agents, each with different mechanisms of action and demonstrating improved overall survival in separate randomized phase 3 trials. Many of these novel agents are now also being evaluated in earlier stages of the disease, which may ultimately lead to even better outcomes. Objective To summarize the current literature on the management of mCRPC with a particular focus on novel chemotherapy approaches, hormonal approaches, immunotherapy, and radiopharmaceuticals showing survival benefits in phase 3 clinical trials. Emerging therapies in late stages of development are also discussed briefly. Evidence acquisition A comprehensive search of PubMed, identified studies pertaining to novel therapies evaluated in mCRPC since the initial approval of docetaxel in 2004. Abstracts from major international meetings were hand searched to identify studies of novel agents in late stage development in mCRPC. The Clinical Trials.gov database was used to find ongoing clinical trials in the area of mCRPC. A detailed search of each new agent was also performed to ensure that additional trials of these agents in other stages of the disease were included where relevant. Evidence synthesis The main agents discussed are the androgen synthesis inhibitor abiraterone acetate, the androgen receptor inhibitor enzalutamide, the novel taxane chemotherapy cabazitaxel, the immunotherapy sipuleucel-T, and the radiopharmaceutical radium 223. Other emerging agents and a brief discussion of negative phase 3 results are also included. Conclusions It is a very exciting time in the field of mCRPC, where therapeutic advances have improved outcomes in this disease, although once metastatic overall median survival remains a dismal 2-3 years. The key now will be to understand how best to use these new agents, understand the mechanisms of resistance to them, continue to develop novel treatment strategies, and ultimately test these agents earlier in the disease when cure may be possible. © 2013 European Association of Urology.


Groot P.J.,California Institute of Technology | Groot P.J.,Radboud University Nijmegen
Astrophysical Journal | Year: 2012

In eclipsing binaries the stellar rotation of the two components will cause a rotational Doppler beaming during eclipse ingress and egress when only part of the eclipsed component is covered. For eclipsing binaries with fast spinning components this photometric analog of the well-known spectroscopic Rossiter-McLaughlin effect can exceed the strength of the orbital effect. Example light curves are shown for a detached double white dwarf binary, a massive O-star binary and a transiting exoplanet case, similar to WASP-33b. Inclusion of the rotational Doppler beaming in eclipsing systems is a prerequisite for deriving the correct stellar parameters from fitting high-quality photometric light curves and can be used to determine stellar obliquities as well as, e.g., an independent measure of the rotational velocity in those systems that may be expected to be fully synchronized. © 2012 The American Astronomical Society. All rights reserved.


Andersen P.K.,Copenhagen University | Geskus R.B.,Academic Medical Center and Public Health Service Amsterdam | De witte T.,Radboud University Nijmegen | Putter H.,Leiden University
International Journal of Epidemiology | Year: 2012

Background In studies of all-cause mortality, the fundamental epidemiological concepts of rate and risk are connected through a well-defined one-to-one relation. An important consequence of this relation is that regression models such as the proportional hazards model that are defined through the hazard (the rate) immediately dictate how the covariates relate to the survival function (the risk).Methods This introductory paper reviews the concepts of rate and risk and their one-to-one relation in all-cause mortality studies and introduces the analogous concepts of rate and risk in the context of competing risks, the cause-specific hazard and the cause-specific cumulative incidence function. Results The key feature of competing risks is that the one-to-one correspondence between cause-specific hazard and cumulative incidence, between rate and risk, is lost. This fact has two important implications. First, the naïve Kaplan-Meier that takes the competing events as censored observations, is biased. Secondly, the way in which covariates are associated with the cause-specific hazards may not coincide with the way these covariates are associated with the cumulative incidence. An example with relapse and non-relapse mortality as competing risks in a stem cell transplantation study is used for illustration. Conclusion The two implications of the loss of one-to-one correspondence between cause-specific hazard and cumulative incidence should be kept in mind when deciding on how to make inference in a competing risks situation. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012.


Jacobs B.,Radboud University Nijmegen
Proceedings - Symposium on Logic in Computer Science | Year: 2013

So-called effect algebras and modules are basic mathematical structures that were first identified in mathematical physics, for the study of quantum logic and quantum probability. They incorporate a double negation law p^{\perp\perp} = p. Since then it has been realised that these effect structures form a useful abstraction that covers not only quantum logic, but also Boolean logic and probabilistic logic. Moreover, the duality between effect and convex structures lies at the heart of the duality between predicates and states. These insights are leading to a uniform framework for the semantics of computation and logic. This framework has been elaborated elsewhere for set-theoretic, discrete probabilistic, and quantum computation. Here the missing case of continuous probability is shown to fit in the same uniform framework. On a technical level, this involves an investigation of the logical aspects of the Giry monad on measurable spaces and of Lebesgue integration. © 2013 IEEE.


Vos P.E.,Radboud University Nijmegen
Critical Care | Year: 2011

Traumatic brain injury (TBI) is a pathologically heterogeneous disease affecting people of all ages. The highest incidence of TBI occurs in young people and the average age is 30 to 40 years. Injury grading may range from mild with a low frequency (1 per 100) of life-threatening intracranial hematoma that needs immediate neurosurgical operation and very low mortality (1 per 1,000) to severe with a high likelihood of life-threatening intracranial hematoma (up to 1 per 3), a 40% case fatality rate and a high disability rate (2 per 3) in survivors. Estimation of the prognosis in severe TBI is currently based on demographic and clinical predictors, including age, Glasgow Coma Scale, pupillary reactions, extracranial injury (hypotension and hypoxia) and computed tomography indices (brain swelling, focal mass lesions, subarachnoid hemorrhage). Biomarkers reflecting damage to neurons and astrocytes may add important complementary information to clinical predictors of outcome and provide insight into the pathophysiology of TBI. © 2011 BioMed Central Ltd.


Li B.,CAS Lanzhou Institute of Chemical Physics | Yu B.,CAS Lanzhou Institute of Chemical Physics | Huck W.T.S.,Radboud University Nijmegen | Liu W.,CAS Lanzhou Institute of Chemical Physics | Zhou F.,CAS Lanzhou Institute of Chemical Physics
Journal of the American Chemical Society | Year: 2013

Surface initiated atom transfer radical polymerization (SI-ATRP) was triggered after diffusion of a CuI/L activator generated at a working electrode. A stable [CuIIL]/[CuIL] ratio gradient was formed at the gap between the working electrode and the initiator terminated substrate due to ion diffusion. The size of the gap can be used to dictate polymer growth kinetics at different gap distances. Gradient polymer brushes were grafted when substrate was placed at a tilting angle along [Cu IIL]/[CuIL] gradient. © 2013 American Chemical Society.


Granic I.,Radboud University Nijmegen
Development and Psychopathology | Year: 2014

The majority of aggressive children exhibit symptoms of anxiety, yet none of our developmental models of aggression incorporate the role of anxiety, and our treatments ignore this comorbidity. This article outlines a novel theoretical model that specifies three hypotheses about comorbid anxious and aggressive children: (a) unpredictable parenting induces anxiety in children that in turn triggers aggressive behavior; (b) prolonged periods of anxiety deplete children's capacity to inhibit impulses and trigger bouts of aggression, and aggression in turn functions to regulate levels of anxiety; and (c) minor daily stressors give rise to anxiety while cognitive perseveration maintains anxious moods, increasingly disposing children to aggress. Little or no research has directly tested these hypotheses. Extant research and theory consistent with these claims are herein reviewed, and future research designs that can test them specifically are suggested. The clinical implications most relevant to the hypotheses are discussed, and to improve the efficacy of treatments for childhood aggression, it is proposed that anxiety may need to be the primary target of treatment. © 2014 Cambridge University Press.


Bahlmann J.,University of Lubeck | Bahlmann J.,University of California at Berkeley | Aarts E.,University of California at Berkeley | D'Esposito M.,University of California at Berkeley | D'Esposito M.,Radboud University Nijmegen
Journal of Neuroscience | Year: 2015

The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands. © 2015 the authors.


Endrass T.,Otto Von Guericke University of Magdeburg | Endrass T.,Center for Behavioral Brain science | Ullsperger M.,Otto Von Guericke University of Magdeburg | Ullsperger M.,Center for Behavioral Brain science | Ullsperger M.,Radboud University Nijmegen
Neuroscience and Biobehavioral Reviews | Year: 2014

Obsessive-compulsive disorder (OCD) is characterized by overactivity in frontal and striatal brain regions, and event-related potential studies have shown increased brain activity during performance monitoring. The error-related negativity (ERN) is a component of the event-related potential that is observed following incorrect responses, and signals the need for behavioral adjustments. ERN enhancements have even been considered as a biomarker or endophenotype of OCD. However over the past years, enhanced ERN amplitudes, although less reliably, were also found in anxiety and affective disorders. These results question the specificity of ERN alterations to OCD. The present review summarizes current findings on performance monitoring and feedback processing in OCD and their relation to behavioral measures. Further, it discusses possible differential mechanisms contributing to amplitude variations in different clinical conditions. © 2014 Elsevier Ltd.


Slota J.E.,University of Cambridge | He X.,University of Cambridge | Huck W.T.S.,University of Cambridge | Huck W.T.S.,Radboud University Nijmegen
Nano Today | Year: 2010

Whilst inspiring significant academic interest, the maximum power conversion efficiencies achieved by polymer PVs under solar conditions (PCE; 6.10-6.77%), are not yet sufficient for the devices to become widely marketable. Therefore much current work in the area is focussed on raising device efficiencies as far as possible towards theoretically achievable levels. To this end, key strategies involve material design and synthesis, device processing, and methods for controlling the morphology of the active components. This review aims to highlight the importance of morphological design and control for highly efficient polymer PVs, to discuss strategies by which morphology can be controlled, and to outline some of the characterisation techniques vital to the understanding and optimisation of morphology in these materials. © 2010 Elsevier Ltd. All rights reserved.


Verhagen A.F.,Radboud University Nijmegen
Interactive cardiovascular and thoracic surgery | Year: 2013

In patients with lung cancer, endosonography has emerged as a minimally invasive method to obtain cytological proof of mediastinal lymph nodes, suspicious for metastases on imaging. In case of a negative result, it is currently recommended that a cervical mediastinoscopy be performed additionally. However, in daily practice, a second procedure is often regarded superfluous. The goal of our study was to assess the additional value of a cervical mediastinoscopy, after a negative result of endosonography, in routine clinical practice. In a retrospective cohort study, the records of 147 consecutive patients with an indication for mediastinal lymph node staging and a negative result of endosonography were analysed. As a subsequent procedure, 124 patients underwent a cervical mediastinoscopy and 23 patients were scheduled for an intended curative resection directly. The negative predictive value (NPV) for both diagnostic procedures was determined, as well as the number of patients who needed to undergo a mediastinoscopy to find one false-negative result of endosonography (number needed to treat (NNT)). Clinical data of patients with a false-negative endosonography were analysed. When using cervical mediastinoscopy as the gold standard, the NPV for endosonography was 88.7%, resulting in a NNT of 8.8 patients. For patients with fluoro-2-deoxyglucose positron emission tomography positive mediastinal lymph nodes, the NNT was 6.1. Overall, a futile thoracotomy could be prevented in 50% of patients by an additional mediastinoscopy. A representative lymph node aspirate, containing adequate numbers of lymphocytes, did not exclude metastases. In patients with a high probability of mediastinal metastases, based on imaging, and negative endosonography, cervical mediastinoscopy should not be omitted, not even when the aspirate seems representative.


Gunkel G.,University of Cambridge | Huck W.T.S.,University of Cambridge | Huck W.T.S.,Radboud University Nijmegen
Journal of the American Chemical Society | Year: 2013

Nonspecific protein adsorption is a central challenge for the use of polymeric materials in biological media. While the quantity of adsorbed protein can be lowered, very few surfaces are protein resistant when exposed to undiluted serum or plasma. The underlying principles of this fouling and the adsorbing proteins remain to be identified. Here, we investigated adsorption from undiluted human blood plasma to three different polymer brushes. Our study showed that the polymer structure does not influence which proteins adsorb. Further, we identified 98 plasma proteins that still foul current "protein-resistant" polymer brushes. Detailed studies into the major adsorbing protein revealed the central role that lipoproteins and low density lipoprotein in particular play in fouling of plasma to polymeric biomaterials. However, although apolipoprotein B100 is found as a major fouling protein in our mass spectrometry screening, studies on individual components of lipoproteins show that it is not apoB100 but a mixture of phospholipids, triglycerides, and cholesteryl esters that plays a major role in lipoprotein adsorption. © 2013 American Chemical Society.


Ullsperger M.,Otto Von Guericke University of Magdeburg | Ullsperger M.,Center for Behavioral Brain science | Ullsperger M.,Radboud University Nijmegen | Fischer A.G.,Otto Von Guericke University of Magdeburg | And 5 more authors.
Trends in Cognitive Sciences | Year: 2014

Successful goal-directed behavior critically depends on performance monitoring, a set of cognitive and affective functions determining whether adaptive control is needed and, if so, which type and magnitude is required. Knowledge of the brain structures involved in such a process has grown enormously, although the time course of performance-monitoring (PM) activity remains poorly understood. Here, we review evidence from EEG recordings in humans and show that monitored events elicit a rather uniform sequence of cortical activity reflecting the detection, accumulation, and weighting of evidence for the necessity to adapt and (re)act. We link the EEG findings with invasive and pharmacological findings and evaluate the neurobiological plausibility of current theories of PM. © 2014 Elsevier Ltd.


Wolters S.A.M.,Radboud University Nijmegen
Communications in Mathematical Physics | Year: 2013

The aim of this paper is to compare the two topos-theoretic approaches to quantum mechanics that may be found in the literature to date. The first approach, which we will call the contravariant approach, was originally proposed by Isham and Butterfield, and was later extended by Döring and Isham. The second approach, which we will call the covariant approach, was developed by Heunen, Landsman and Spitters. Motivated by coarse-graining and the Kochen-Specker theorem, the contravariant approach uses the topos of presheaves on a specific context category, defined as the poset of commutative von Neumann subalgebras of some given von Neumann algebra. In particular, the approach uses the spectral presheaf. The intuitionistic logic of this approach is given by the (complete) Heyting algebra of closed open subobjects of the spectral presheaf. We show that this Heyting algebra is, in a natural way, a locale in the ambient topos, and compare this locale with the internal Gelfand spectrum of the covariant approach. In the covariant approach, a non-commutative C*-algebra (in the topos Set) defines a commutative C*-algebra internal to the topos of covariant functors from the context category to the category of sets. We give an explicit description of the internal Gelfand spectrum of this commutative C*-algebra, from which it follows that the external spectrum is spatial. Using the daseinisation of self-adjoint operators from the contravariant approach, we give a new definition of the daseinisation arrow in the covariant approach and compare it with the original version. States and state-proposition pairing in both approaches are compared. We also investigate the physical interpretation of the covariant approach. © 2012 Springer-Verlag Berlin Heidelberg.


Heskes T.,Radboud University Nijmegen
Nature Reviews Genetics | Year: 2016

The rapid increase in loci discovered in genome-wide association studies has created a need to understand the biological implications of these results. Gene-set analysis provides a means of gaining such understanding, but the statistical properties of gene-set analysis are not well understood, which compromises our ability to interpret its results. In this Analysis article, we provide an extensive statistical evaluation of the core structure that is inherent to all gene- set analyses and we examine current implementations in available tools. We show which factors affect valid and successful detection of gene sets and which provide a solid foundation for performing and interpreting gene-set analysis. © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Katsnelson M.I.,Radboud University Nijmegen
Journal of Computational and Theoretical Nanoscience | Year: 2011

Charge carriers in graphene are chiral quasiparticles ("massless Dirac fermions"). Graphene provides therefore an amazing opportunity to study subtle quantum relativistic effects in condensed matter experiment. Here I review a theory of one of these unusual features of graphene, a "pseu-dodiffusive" transport in the limit of zero charge carrier concentration, which is related to existence of zero-modes of the Dirac operator and to the Zitterbewegung of unltrarelativistic particles. A confor-mal mapping technique is a powerful mathematical tool to study these phenomena, as demonstrated here, using the Aharonov-Bohm effect in graphene rings with Corbino geometry as an example. Copyright © 2011 American Scientific Publishers All rights reserved.


Van De Meerakker S.Y.T.,Radboud University Nijmegen | Bethlem H.L.,VU University Amsterdam | Vanhaecke N.,University Paris - Sud | Meijer G.,Fritz Haber Institute
Chemical Reviews | Year: 2012

A study was conducted to demonstrate the manipulation of molecular beams with electric and magnetic fields. Seeded pulsed supersonic expansions were employed to conduct the investigations. The conservative forces exerted further downstream by the electric and magnetic fields enabled the researchers to manipulate and control the shape and the position of the distribution in the six-dimensional phase-space. All of the original experimental geometries were devised to create strong magnetic or electric field gradients to efficiently deflect particles from the beam axis. It was demonstrated that a detailed understanding of the influence of the external field on the energy level structure of the molecules was required for the manipulation of molecules with electric or magnetic fields.


Low T.,IBM | Jiang Y.,Zhejiang Normal University | Jiang Y.,Purdue University | Katsnelson M.,Radboud University Nijmegen | Guinea F.,CSIC - Institute of Materials Science
Nano Letters | Year: 2012

The combination of high-frequency vibrations and metallic transport in graphene makes it a unique material for nanoelectromechanical devices. In this Letter, we show that graphene-based nanoelectromechanical devices are extremely well suited for charge pumping due to the sensitivity of its transport coefficients to perturbations in electrostatic potential and mechanical deformations, with the potential for novel small scale devices with useful applications. © 2012 American Chemical Society.


van der Kolk N.M.,Radboud University Nijmegen | King L.A.,Oregon Health And Science University
Movement Disorders | Year: 2013

Parkinson's disease is a prevalent neurodegenerative disorder for which only symptomatic treatment exists. Gait and balance disturbance is common in Parkinson's disease and is a major contributor to increased disability and decreased health-related quality of life and survival. Balance and gait deficits in Parkinson's disease are notoriously difficult to treat and are not significantly helped by pharmacological or surgical treatment. The last two decades have seen a dramatic increase in the research and clinical interest in using exercise as a treatment for mobility problems in people with Parkinson's disease. With exciting advances in basic science research suggesting neurochemical and neuroplastic changes after exercise, an increasing number of high-quality studies are documenting particular aspects of mobility improving after exercise. Exercise has the potential to help both motor (gait, balance, strength) and nonmotor (depression, apathy, fatigue, constipation) aspects of Parkinson's disease as well as secondary complications of immobility (cardiovascular, osteoporosis). This perspective article focuses primarily on recent evidence on the effects of exercise in improving mobility while highlighting the importance of targeted exercise intervention for maximizing the benefits of exercise. Suggestions for exercise guidelines, adherence issues, and directions for future research are provided. © 2013 Movement Disorder Society.


Wehling T.O.,University of Hamburg | SasIoglu E.,Julich Research Center | Friedrich C.,Julich Research Center | Lichtenstein A.I.,University of Hamburg | And 2 more authors.
Physical Review Letters | Year: 2011

To obtain an effective many-body model of graphene and related materials from first principles we calculate the partially screened frequency dependent Coulomb interaction. In graphene, the effective on-site (Hubbard) interaction is U00=9.3eV in close vicinity to the critical value separating conducting graphene from an insulating phase emphasizing the importance of nonlocal Coulomb terms. The nearest-neighbor Coulomb interaction strength is computed to U01=5.5eV. In the long-wavelength limit, we find the effective background dielectric constant of graphite to be ε=2.5 in very good agreement with experiment. © 2011 American Physical Society.


Janssen T.,Radboud University Nijmegen
Symmetry | Year: 2014

An overview is given of the use of symmetry considerations for aperiodic crystals. Superspace groups were introduced in the seventies for the description of incommensurate modulated phases with one modulation vector. Later, these groups were also used for quasi-periodic crystals of arbitrary rank. Further extensions use time reversal and time translation operations on magnetic and electrodynamic systems. An alternative description of magnetic structures to that with symmetry groups, the Shubnikov groups, is using representations of space groups. The same can be done for aperiodic crystals. A discussion of the relation between the two approaches is given. Representations of space groups and superspace groups play a role in the study of physical properties. These, and generalizations of them, are discussed for aperiodic crystals. They are used, in particular, for the characterization of phase transitions between aperiodic crystal phases. © 2014 by the author.


Jacquemyn H.,Catholic University of Leuven | de Meester L.,Charles University | Jongejans E.,Radboud University Nijmegen | Honnay O.,Catholic University of Leuven
Journal of Ecology | Year: 2012

1. The effects of habitat fragmentation on plant population genetic structure and diversity are relatively well studied. Yet, most of these studies used molecular tools focusing on neutral genetic markers, and much less is known about the potential evolutionary consequences of habitat fragmentation on ecologically relevant plant traits. 2. It can be expected that the altered biotic and abiotic conditions and limited gene flow following habitat fragmentation may impose strong selection pressures on traits important for plant fitness. Responses to these selection pressures may, however, be hampered by reduced genetic diversity through genetic drift. Conversely, evolutionary changes in flower or dispersal traits may itself impact the strength of inbreeding and genetic drift. 3. In this review, we highlight different reproductive plant traits that may be under selection following habitat fragmentation, and we examine studies that have shown indications for rapid evolutionary responses. 4. There are still relatively few studies that have convincingly shown that habitat fragmentation generates rapid evolutionary responses. Separating genetic from plastic trait responses and quantifying the long-term fitness consequences of evolutionary changes in plant traits also remain major challenges. 5. Synthesis. Many plant traits may be subject to selection following habitat fragmentation, but, until now, studies that quantified evolutionary responses to habitat fragmentation are limited. To study the consequences of changing plant traits for population fitness, we advocate applying population models that link demographic vital rates, the responding plant traits and their heritability. © 2012 The Authors. Journal of Ecology © 2012 British Ecological Society.


Geurts Van Kessel A.,Radboud University Nijmegen
Cellular Oncology | Year: 2014

The 2014 joint meeting of the International Society for Cellular Oncology (ISCO) and the European Workshop on Cytogenetics and Molecular Genetics of Solid Tumors (EWCMST), organized by Nick Gilbert, Juan Cigudosa and Bauke Ylstra, was held from 11 to 14 May in Malaga, Spain. Since the previous meeting in 2012, the ever increasing availability of new sequencing technologies has enabled the analysis of cancer genomes at an increasingly greater detail. In addition to structural changes in the genome (i.e., translocations, deletions, amplifications), frequent mutations in important regulatory genes have been found to occur, as also frequent alterations in a large number of epigenetic factors. The challenge now is to relate structural changes in cancer genomes to the underlying disease mechanisms and to reveal opportunities for the design of novel (targeted) therapies. During the meeting, various topics related to these challenges and opportunities were addressed, including those dealing with functional genomics, genome instability, biomarkers and diagnostics, cancer genetics and epigenomics. Special attention was paid to therapy-driven cancer evolution (keynote lecture) and relationships between DNA repair, cancer and ageing (Prof. Ploem lecture). Based on the information presented at the meeting, several aspects of the cancer genome and its functional implications are provided in this report. © 2014 International Society for Cellular Oncology.


Rubtsov A.N.,Moscow State University | Katsnelson M.I.,Radboud University Nijmegen | Lichtenstein A.I.,University of Hamburg
Annals of Physics | Year: 2012

We develop a general theory of a boson decomposition for both local and non-local interactions in lattice fermion models which allows us to describe fermionic degrees of freedom and collective charge and spin excitations on equal footing. An efficient perturbation theory in the interaction of the fermionic and the bosonic degrees of freedom is constructed in the so-called dual variables in the path-integral formalism. This theory takes into account all local correlations of fermions and collective bosonic modes and interpolates between itinerant and localized regimes of electrons in solids. The zero-order approximation of this theory corresponds to an extended dynamical mean-field theory (EDMFT), a regular way to calculate nonlocal corrections to EDMFT is provided. It is shown that dual ladder summation gives a conserving approximation beyond EDMFT. The method is especially suitable for consideration of collective magnetic and charge excitations and allows to calculate their renormalization with respect to "bare" RPA-like characteristics. General expression for the plasmonic dispersion in correlated media is obtained. As an illustration it is shown that effective superexchange interactions in the half-filled Hubbard model can be derived within the dual-ladder approximation. © 2012 Elsevier Inc.


Knoop H.,Radboud University Nijmegen | Van Kessel K.,University of Auckland | Moss-Morris R.,University of Southampton
Psychological Medicine | Year: 2012

Background Chronic fatigue is a common symptom of multiple sclerosis (MS). A randomized controlled trial (RCT) showed that cognitive behavioural therapy (CBT) was more effective in reducing MS fatigue than relaxation training (RT). The aim of the current study was to analyse additional data from this trial to determine whether (1) CBT compared to RT leads to significantly greater changes in cognitions and behaviours hypothesized to perpetuate MS fatigue; (2) changes in these variables mediate the effect of CBT on MS fatigue; and (3) these mediation effects are independent of changes in mood.Method Seventy patients (CBT, n=35; RT, n=35) completed the Cognitive and Behavioural Responses to Symptoms Questionnaire (CBSQ), the Brief Illness Perception Questionnaire (B-IPQ) modified to measure negative representations of fatigue, the Hospital Anxiety and Depression Scale (HADS), and the Chalder Fatigue Questionnaire (CFQ), pre- and post-therapy. Multiple mediation analysis was used to determine which variables mediated the change in fatigue.Results Avoidance behaviour and three cognitive variables (symptom focusing, believing symptoms are a sign of damage and a negative representation of fatigue) improved significantly more in the CBT than the RT group. Mediation analysis showed that changing negative representations of fatigue mediated the decrease in severity of fatigue. Change in anxiety covaried with reduction in fatigue but the mediation effect for negative representations of fatigue remained when controlling for improvements in mood.Conclusions Change in beliefs about fatigue play a crucial role in CBT for MS fatigue. These beliefs and the role of anxiety deserve more attention in the further development of this intervention. © 2011 Cambridge University Press.


Boelens W.C.,Radboud University Nijmegen
Progress in Biophysics and Molecular Biology | Year: 2014

αB-crystallin, also called HspB5, is a molecular chaperone able to interact with unfolding proteins. By interacting, it inhibits further unfolding, thereby preventing protein aggregation and allowing ATP-dependent chaperones to refold the proteins. αB-crystallin belongs to the family of small heat-shock proteins (sHsps), which in humans consists of 10 different members. The protein forms large oligomeric complexes, containing up to 40 or more subunits, which invivo consist of heterooligomeric complexes formed by a mixture of αB-crystallin and other sHsps. αB-crystallin is highly expressed in the lens and to a lesser extent in several other tissues, among which heart, skeletal muscle and brain. αB-crystallin plays a role in several cellular processes, such as signal transduction, protein degradation, stabilization of cytoskeletal structures and apoptosis. Mutations in the αB-crystallin gene can have detrimental effects, leading to pathologies such as cataract and cardiomyopathy. This review describes the biological roles of αB-crystallin, with a special focus on its function in the eye lens, heart muscle and brain. In addition its therapeutic potential is discussed. © 2014 Elsevier Ltd.


Lionakis M.S.,National Institute of Allergy and Infectious Diseases | Netea M.G.,Radboud University Nijmegen | Holland S.M.,National Institute of Allergy and Infectious Diseases
Cold Spring Harbor Perspectives in Medicine | Year: 2014

A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.


Knijn N.,Radboud University Nijmegen
Discovery medicine | Year: 2010

Currently used cytotoxic drugs in the treatment of advanced colorectal cancer (ACC) are primarily the fluoropyrimidines, irinotecan, and oxaliplatin. The introduction of targeted therapy has increased the therapeutic arsenal. Two classes of monoclonal antibodies have been approved for clinical use in ACC: bevacizumab, an antibody against the vascular endothelial growth factor (VEGF), and cetuximab and panitumumab, antibodies against the epidermal growth factor receptor (EGFR). We review the current status of targeted therapy and the mechanism of action of monoclonal antibodies in ACC.


Hendriks W.J.A.J.,Radboud University Nijmegen | Pulido R.,Biocruces Health Research Institute | Pulido R.,Ikerbasque
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

Reversible tyrosine phosphorylation of proteins is a key regulatory mechanism to steer normal development and physiological functioning of multicellular organisms. Phosphotyrosine dephosphorylation is exerted by members of the super-family of protein tyrosine phosphatase (PTP) enzymes and many play such essential roles that a wide variety of hereditary disorders and disease susceptibilities in man are caused by PTP alleles. More than two decades of PTP research has resulted in a collection of PTP genetic variants with corresponding consequences at the molecular, cellular and physiological level. Here we present a comprehensive overview of these PTP gene variants that have been linked to disease states in man. Although the findings have direct bearing for disease diagnostics and for research on disease etiology, more work is necessary to translate this into therapies that alleviate the burden of these hereditary disorders and disease susceptibilities in man. © 2013 The Authors.


Demmel M.,University of Mainz | Saueressig F.,Radboud University Nijmegen | Zanusso O.,Friedrich - Schiller University of Jena
Annals of Physics | Year: 2015

We construct a novel Wetterich-type functional renormalization group equation for gravity which encodes the gravitational degrees of freedom in terms of gauge-invariant fluctuation fields. Applying a linear-geometric approximation the structure of the new flow equation is considerably simpler than the standard Quantum Einstein Gravity construction since only transverse-traceless and trace part of the metric fluctuations propagate in loops. The geometric flow reproduces the phase-diagram of the Einstein-Hilbert truncation including the non-Gaussian fixed point essential for Asymptotic Safety. Extending the analysis to the polynomial f(R)-approximation establishes that this fixed point comes with similar properties as the one found in metric Quantum Einstein Gravity; in particular it possesses three UV-relevant directions and is stable with respect to deformations of the regulator functions by endomorphisms. © 2015 Elsevier Inc.


Cavalli G.,San Raffaele Scientific Institute | Dinarello C.A.,Radboud University Nijmegen
Rheumatology (Oxford, England) | Year: 2015

The inflammatory cytokines IL-1α and IL-1β orchestrate local and systemic inflammatory responses underlying a broad spectrum of diseases. Three agents for reducing IL-1 activities are currently available. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist. Anakinra binds to the IL-1 receptor and prevents the activity of IL-1α and IL-1β. The soluble decoy receptor rilonacept and the neutralizing mAb canakinumab block IL-1β. A mAb directed against the IL-1 receptor and a neutralizing anti-human IL-1α are in clinical trials. The availability of therapies specifically targeting IL-1 unveiled the pathological role of IL-1-mediated inflammation in a broadening list of diseases. Conditions effectively treated with agents blocking IL-1 range from classic rheumatic diseases, such as RA and gout, to autoinflammatory syndromes, such as systemic JIA and FMF. However, IL-1 antagonism is also effective against highly prevalent inflammatory diseases, namely cardiovascular diseases and type 2 diabetes, conditions that are frequently encountered as co-morbidities in patients with rheumatic diseases. Thereby, IL-1 inhibition has the potential to lift the burden of disease for patients with rheumatic conditions, but also to provide clinical benefits beyond the efficacy on osteoarticular manifestations. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.


Homberg J.R.,Radboud University Nijmegen | Molteni R.,University of Milan | Calabrese F.,University of Milan | Riva M.A.,University of Milan
Neuroscience and Biobehavioral Reviews | Year: 2014

Serotonin (5-HT) and brain-derived neurotrophin factor (BDNF) are known to modulate behavioral responses to stress and to mediate the therapeutic efficacy of antidepressant agents through neuroplastic and epigenetic mechanisms. While the two systems interact at several levels, this scenario is complicated by a number of variants including brain region specificity, 5-HT receptor selectivity and timing. Based on recent insights obtained using 5-HT transporter (5-HTT) knockout rats we here set-out and discuss the crucial role of neurodevelopmental mechanisms and the contribution of transcription factors and epigenetic modifications to this interaction and its variants. 5-HTT knockout in rats, as well as the low activity short allelic variant of the serotonin transporter human polymorphism, consistently show reduced BDNF mRNA and protein levels in the hippocampus and in the prefrontal cortex. This starts during the second postnatal week, is preceded by DNA hypermethylation during the first postnatal week, and it is developmentally paralleled by reduced expression of key transcription factors. The reduced BDNF levels, in turn, affect 5-HT1A receptor-mediated intracellular signaling and thereby the serotonergic phenotype of the neurons. We propose that such a negative spiral of modifications may affect brain development and reduce its resiliency to environmental challenges during critical time windows, which may lead to phenotypic alterations that persist for the entire life. The characterization of 5-HT-BDNF interactions will eventually increase the understanding of mental illness etiology and, possibly, lead to the identification of novel molecular targets for drug development. © 2014 Elsevier Ltd.


Van Vugt R.,Radboud University Nijmegen
The Cochrane database of systematic reviews | Year: 2013

Trauma is the fifth leading cause of death worldwide, and in people younger than 40 years of age, it is the leading cause of death. During the resuscitation of trauma patients at the emergency department, there are two different commonly used diagnostic strategies. Conventionally, there is the use of physical examination and conventional diagnostic imaging, potentially followed by selective use of computed tomography (CT). Alternatively, there is the use of physical examination and conventional diagnostics, followed by a routine (instead of selective) use of thoracoabdominal CT. It is currently unknown which of the two strategies is the better diagnostic strategy for patients with blunt high-energy trauma. To assess the effects of routine thoracoabdominal CT compared with selective thoracoabdominal CT on mortality in blunt high-energy trauma patients. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (Issue 4, 2013); MEDLINE (OvidSP), EMBASE (OvidSP) and CINAHL for all published randomised controlled trials (RCTs). We did not restrict the searches by language, date or publication status. We conducted the search on the 9 May 2013. We included RCTs of trauma resuscitation algorithms using routine thoracoabdominal CT versus algorithms using selective CT in this review. We included all blunt high-energy trauma patients (including blast or barotrauma). Two authors independently evaluated the search results. The systematic search identified 481 references; after removal of duplicates, 396 remained. We found no RCTs comparing routine versus selective thoracoabdominal CT in blunt high-energy trauma patients. We excluded 381 studies based on the abstracts of the publications because of irrelevance to the review topic, and a further 15 studies after full-text evaluation. We found no RCTs of routine versus selective thoracoabdominal CT in patients with blunt high-energy trauma. Based on the lack of evidence from RCTs, it is not possible to say which approach is better in reducing deaths.


van Eijk J.,Radboud University Nijmegen
The Cochrane database of systematic reviews | Year: 2013

Idiopathic lumbosacral plexopathy (ILSP), also called lumbosacral plexitis or non-diabetic lumbosacral (radiculo)plexus neuropathy is a rare clinical entity. The core features are (sub)acute, severe, asymmetrical leg pain, followed by asymmetrical multifocal weakness and atrophy in the subsequent weeks or months. Sensory symptoms include paresthesias, hypesthesia, allodynia, and autonomic dysfunction. ILSP generally runs a monophasic and self limiting course. Recovery starts slowly over months to several years and is nearly always incomplete. Some studies suggest that the condition has an immune-mediated etiology. Biopsies of distal cutaneous nerve segments have shown features suggestive of an inflammatory microvasculitis causing ischemic damage of the nerves. The clinical and pathological findings are similar to those found in diabetic lumbosacral plexus neuropathy and suggest that inflammation may form part of the final common pathway in both conditions. To assess the effects of any form of immunotherapy in the treatment of ILSP. On 15 October 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and Index to Theses. We scanned conference abstracts, and searched trials databases for ongoing trials. We checked all references in the identified trials and contacted authors to identify any additional published or unpublished data. We intended to include all randomized controlled trials (RCTs) or quasi-RCTs of any immunotherapy given within six weeks of disease onset, in participants with conditions fulfilling all the following: acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs, weakness that is not confined to one nerve or nerve root distribution, electrophysiological tests showing predominantly axonal neuropathies, exclusion of other causes of lumbosacral radiculopathy and plexopathy as well as patients with plasma sugar in the diabetic range (fasting greater than 7.0 mmol/L, random greater than 11.1 mmol/L). Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria, according to standard Cochrane methodology. We identified no RCTs of any immunotherapy for ILSP. There is at present no evidence from randomized trials to support any recommendation on the use of any immunotherapy treatment in ILSP.


Huisman T.J.,Radboud University Nijmegen
Nature Nanotechnology | Year: 2016

The idea to use not only the charge but also the spin of electrons in the operation of electronic devices has led to the development of spintronics, causing a revolution in how information is stored and processed. A novel advancement would be to develop ultrafast spintronics using femtosecond laser pulses. Employing terahertz (1012 Hz) emission spectroscopy and exploiting the spin–orbit interaction, we demonstrate the optical generation of electric photocurrents in metallic ferromagnetic heterostructures at the femtosecond timescale. The direction of the photocurrent is controlled by the helicity of the circularly polarized light. These results open up new opportunities for realizing spintronics in the unprecedented terahertz regime and provide new insights in all-optical control of magnetism. © 2016 Nature Publishing Group


Recent scholarship grounded in strategic-relational state theory has offered a compelling approach to state spatial restructuring under neoliberal capitalism. By drawing on Hungary's post-1990 state spatial reforms, this paper discusses a major limitation of state theoretical frameworks. In particular, the paper seeks to challenge state theorists' generally subtle but persistent bias to capitalist economic structures, and argues that the above bias impedes an adequate and effectively critical account of state spatial regulation. Finally, it makes a case for a perspective on new state spaces that acknowledges the wider socio-historical embeddedness of state space production, as well as its inherently political nature. © 2010 The Author Journal compilation © 2010 Editorial Board of Antipode.


Hannink G.,Radboud University Nijmegen
Systematic reviews | Year: 2013

Compared to subgroup analyses in a single study or in a traditional meta-analysis, an individual patient data meta-analysis (IPDMA) offers important potential advantages. We studied how many IPDMAs report on surgical interventions, how many of those surgical IPDMAs perform subgroup analyses, and whether these subgroup analyses have changed decision-making in clinical practice. Surgical IPDMAs were identified using a comprehensive literature search. The last search was conducted on 24 April 2012. For each IPDMA included, we obtained information using a standardized data extraction form, and the quality of reporting was assessed. We also checked whether results were implemented in clinical guidelines. Of all 583 identified IPDMAs, 22 (4%) reported on a surgical intervention. Eighteen (82%) of these IPDMAs presented subgroup analyses. Subgroups were mainly based on patient and disease characteristics. The median number of reported subgroup analyses was 3.5 (IQR 1.25-6.5). Statistical methods for subgroup analyses were mentioned in 11 (61%) surgical IPDMAs.Eleven (61%) of the 18 IPDMAs performing subgroup analyses reported a significant overall effect estimate, whereas six (33%) reported a non-significant one. Of the IPDMAs that reported non-significant overall results, three IPDMAs (50%) reported significant results in one or more subgroup analyses. Results remained significant in one or more subgroups in eight of the IPDMAs (73%) that reported a significant overall result.Eight (44%) of the 18 significant subgroups appeared to be implemented in clinical guidelines. The quality of reporting among surgical IPDMAs varied from low to high quality. Many of the surgical IPDMAs performed subgroup analyses, but overall treatment effects were more often emphasized than subgroup effects. Although, most surgical IPDMAs included in the present study have only recently been published, about half of the significant subgroups were already implemented in treatment guidelines.


Klooster K.,University of Groningen | Ten Hacken N.H.T.,University of Groningen | Hartman J.E.,University of Groningen | Kerstjens H.A.M.,University of Groningen | And 2 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. To date, the benefits have been modest but have been hypothesized to be much larger in patients without interlobar collateral ventilation than in those with collateral ventilation. METHODS We randomly assigned patients with severe emphysema and a confirmed absence of collateral ventilation to bronchoscopic endobronchial-valve treatment (EBV group) or to continued standard medical care (control group). Primary outcomes were changes from baseline to 6 months in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and 6-minute walk distance. RESULTS Eighty-four patients were recruited, of whom 16 were excluded because they had collateral ventilation (13 patients) or because lobar segments were inaccessible to the endobronchial valves (3 patients). The remaining 68 patients (mean [±SD] age, 59±9 years; 46 were women) were randomly assigned to the EBV group (34 patients) or the control group (34). At baseline, the FEV1 and FVC were 29±7% and 77±18% of the predicted values, respectively, and the 6-minute walk distance was 374±86 m. Intention-to-treat analyses showed significantly greater improvements in the EBV group than in the control group from baseline to 6 months: the increase in FEV1 was greater in the EBV group than in the control group by 140 ml (95% confidence interval [CI], 55 to 225), the increase in FVC was greater by 347 ml (95% CI, 107 to 588), and the increase in the 6-minute walk distance was greater by 74 m (95% CI, 47 to 100) (P<0.01 for all comparisons). By 6 months, 23 serious adverse events had been reported in the EBV group, as compared with 5 in the control group (P<0.001). One patient in the EBV group died. Serious treatmentrelated adverse events in this group included pneumothorax (18% of patients) and events requiring valve replacement (12%) or removal (15%). CONCLUSIONS Endobronchial-valve treatment significantly improved pulmonary function and exercise capacity in patients with severe emphysema characterized by an absence of interlobar collateral ventilation. Copyright © 2015 Massachusetts Medical Society. All rights reserved.


Quik J.T.K.,Wageningen University | van De Meent D.,Radboud University Nijmegen | van De Meent D.,National Institute of Public Health and the Environment RIVM | Koelmans A.A.,Wageningen University
Water Research | Year: 2014

Parameters and simplified model approaches for describing the fate of engineered nanoparticles (ENPs) are crucial to advance the risk assessment of these materials. Sedimentation behavior of ENPs in natural waters has been shown to follow apparent first order behavior, a 'black box' phenomenon that is insufficiently understood and therefore of limited applicability. Here we use a detailed Smoluchowski-Stokes model that accounts for homo- and heteroaggregation and sedimentation of ENPs and natural colloids (NCs), to simulate and interpret experimental ENP aggregation-sedimentation data. The model adequately simulated the observed time and initial concentration dependence of CeO2 settling data, and also predicted the conditions for aggregation rate-limitations of overall removal. Heteroaggregation with natural colloids was identified as the dominating removal process. Finally, the empirical apparent first order model data were calibrated against the mechanistic Smoluchowski-Stokes model simulation data, showing excellent fits for a range of NC initial concentrations. Using first order removal rates thus can be considered a valid and informed approximation when modeling ENP fate in the aquatic environment. © 2014 Elsevier Ltd.


Van Der Helm P.A.,Radboud University Nijmegen
Cognitive Processing | Year: 2012

What, if anything, is cognitive architecture and how is it implemented in neural architecture? Focusing on perceptual organization, this question is addressed by way of a pluralist approach which, supported by metatheoretical considerations, combines complementary insights from representational, connectionist, and dynamic systems approaches to cognition. This pluralist approach starts from a representationally inspired model which implements the intertwined but functionally distinguishable subprocesses of feedforward feature encoding, horizontal feature binding, and recurrent feature selection. As sustained by areview of neuroscientific evidence, these are the subprocesses that are believed to take place in the visual hierarchy in the brain. Furthermore, the model employs a special form of processing, called transparallel processing, whose neural signature is proposed to be gamma-band synchronization in transient horizontal neural assemblies. In neuroscience, such assemblies are believed to mediate binding of similar features. Their formal counterparts in the model are special input-dependent distributed representations, called hyperstrings, which allow many similar features to be processed in a transparallel fashion, that is, simultaneously as if only one feature were concerned. This form of processing does justice to both the high combinatorial capacity and the high speed of the perceptual organization process. A naturally following proposal is that those temporarily synchronized neural assemblies are ''gnosons'', that is, constituents of flexible self-organizing cognitive architecture in between the relatively rigid level of neurons and the still elusive level of consciousness. © 2011 The Author (s).


Van Rooij I.,Radboud University Nijmegen
Topics in Cognitive Science | Year: 2012

Four articles in this issue of topiCS (volume 4, issue 1) argue against a computational approach in cognitive science in favor of a dynamical approach. I concur that the computational approach faces some considerable explanatory challenges. Yet the dynamicists' proposal that cognition is self-organized seems to only go so far in addressing these challenges. Take, for instance, the hypothesis that cognitive behavior emerges when brain and body (re-)configure to satisfy task and environmental constraints. It is known that for certain systems of constraints, no procedure can exist (whether modular, local, centralized, or self-organized) that reliably finds the right configuration in a realistic amount of time. Hence, the dynamical approach still faces the challenge of explaining how self-organized constraint satisfaction can be achieved by human brains and bodies in real time. In this commentary, I propose a methodology that dynamicists can use to try to address this challenge. © 2012 Cognitive Science Society, Inc.


Arons A.M.M.,Radboud University Nijmegen | Krabbe P.F.M.,University of Groningen
Expert Review of Pharmacoeconomics and Outcomes Research | Year: 2013

Interest is rising in measuring subjective health outcomes, such as treatment outcomes that are not directly quantifiable (functional disability, symptoms, complaints, side effects and health-related quality of life). Health economists in particular have applied probabilistic choice models in the area of health evaluation. They increasingly use discrete choice models based on random utility theory to derive values for healthcare goods or services. Recent attempts have been made to use discrete choice models as an alternative method to derive values for health states. In this article, various probabilistic choice models are described according to their underlying theory. A historical overview traces their development and applications in diverse fields. The discussion highlights some theoretical and technical aspects of the choice models and their similarity and dissimilarity. The objective of the article is to elucidate the position of each model and their applications for health-state valuation. © 2013 Alexander M Arons.


Levinson S.C.,Max Planck Institute for Psycholinguistics | Levinson S.C.,Radboud University Nijmegen | Holler J.,Max Planck Institute for Psycholinguistics
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

One reason for the apparent gulf between animal and human communication systems is that the focus has been on the presence or the absence of language as a complex expressive system built on speech. But language normally occurs embedded within an interactional exchange of multi-modal signals. If this larger perspective takes central focus, then it becomes apparent that human communication has a layered structure, where the layers may be plausibly assigned different phylogenetic and evolutionary origins-especially in the light of recent thoughts on the emergence of voluntary breathing and spoken language. This perspective helps us to appreciate the different roles that the different modalities play in human communication, as well as how they function as one integrated system despite their different roles and origins. It also offers possibilities for reconciling the 'gesture-first hypothesis' with that of gesture and speech having evolved together, hand in hand-or hand in mouth, rather-as one system. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Ambjorn J.,Copenhagen University | Ambjorn J.,Radboud University Nijmegen | Glaser L.,Copenhagen University | Sato Y.,Nagoya University | Watabiki Y.,Tokyo Institute of Technology
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

Causal Dynamical Triangulations (CDT) is a lattice theory where aspects of quantum gravity can be studied. Two-dimensional CDT can be solved analytically and the continuum (quantum) Hamiltonian obtained. In this Letter we show that this continuum Hamiltonian is the one obtained by quantizing two-dimensional projectable Hořava-Lifshitz gravity. © 2013.


Bosman G.J.C.G.M.,Radboud University Nijmegen
Frontiers in Physiology | Year: 2013

The currently available data suggest that efforts toward improving the quality of red blood cell (RBC) blood bank products should concentrate on: (1) preventing the removal of a considerable fraction of the transfused RBCs that takes place within the first hours after transfusion; (2) minimizing the interaction of the transfused RBCs with the patient's immune system. These issues are important in reducing the number and extent of the damaging side effects of transfusions, such as generation of alloantibodies and autoantibodies and iron accumulation, especially in transfusion-dependent patients. Thus, it becomes important for blood bank research not only to assess the classical RBC parameters for quality control during storage, but even more so to identify the parameters that predict RBC survival, function and behavior in the patient after transfusion. These parameters are likely to result from elucidation of the mechanisms that underly physiological RBC aging in vivo, and that lead to the generation of senescent cell antigens and the accumulation of damaged molecules in vesicles. Also, study of RBC pathology-related mechanisms, such as encountered in various hemoglobinopathies and membranopathies, may help to elucidate the mechanisms underlying a storage-associated increase in susceptibility to physiological stress conditions. Recent data indicate that a combination of new approaches in vitro to mimick RBC behavior in vivo, the growing knowledge of the signaling networks that regulate RBC structure and function, and the rapidly expanding set of proteomic and metabolomic data, will be instrumental to identify the storage-associated processes that control RBC survival after transfusion. © 2013 Bosman.


de Leeuw N.,Radboud University Nijmegen
European Journal of Human Genetics | Year: 2015

Cerebral visual impairment (CVI) is a major cause of low vision in children due to impairment in projection and/or interpretation of the visual input in the brain. Although acquired causes for CVI are well known, genetic causes underlying CVI are largely unidentified. DNAs of 25 patients with CVI and intellectual disability, but without acquired (eg, perinatal) damage, were investigated by whole-exome sequencing. The data were analyzed for de novo, autosomal-recessive, and X-linked variants, and subsequently classified into known, candidate, or unlikely to be associated with CVI. This classification was based on the Online Mendelian Inheritance in Man database, literature reports, variant characteristics, and functional relevance of the gene. After classification, variants in four genes known to be associated with CVI (AHDC1, NGLY1, NR2F1, PGAP1) in 5 patients (20%) were identified, establishing a conclusive genetic diagnosis for CVI. In addition, in 11 patients (44%) with CVI, variants in one or more candidate genes were identified (ACP6, AMOT, ARHGEF10L, ATP6V1A, DCAF6, DLG4, GABRB2, GRIN1, GRIN2B, KCNQ3, KCTD19, RERE, SLC1A1, SLC25A16, SLC35A2, SOX5, UFSP2, UHMK1, ZFP30). Our findings show that diverse genetic causes underlie CVI, some of which will provide insight into the biology underlying this disease process.European Journal of Human Genetics advance online publication, 9 September 2015; doi:10.1038/ejhg.2015.186. © 2015 Macmillan Publishers Limited


Alves Cardoso D.,Radboud University Nijmegen
Journal of biomedical materials research. Part B, Applied biomaterials | Year: 2012

In the past two decades, nanotechnology has entered the field of regenerative medicine, resulting in the development of a novel generation of instructive, nanostructured biomaterials that are able to orchestrate cellular behavior by presenting specific morphological and biological cues. Using nanotechnology, materials containing nanosized features (e.g., pores, patterns, textures, grain sizes) can be obtained that exhibit properties that are considerably altered compared with micron-structured materials. Inspired by the hierarchical nanostructure of bone, the application of nanostructured materials for bone regeneration is gaining increasing interest in the field of biomaterials research. Because crystallographic and chemical studies have shown that synthetic hydroxyapatite closely resembles the inorganic phase found in bone and teeth, synthesis and applications of nanostructured calcium phosphate ceramics have been reviewed. Synthesis techniques for the preparation of calcium phosphate nanoparticles include precipitation, sol-gel, and hydrothermal processes, whereas four main biomedical applications of nanostructured calcium phosphate ceramics in bone regeneration have been addressed in more detail, that is, (1) polymer/calcium phosphate nanocomposites, (2) nanostructured monophasic calcium phosphate bone fillers, (3) nanostructured precursor phases for calcium phosphate cements, and (4) nanostructured calcium phosphate coatings. Copyright © 2012 Wiley Periodicals, Inc.


Venkatachalam R.,Radboud University Nijmegen
Cancer genetics and cytogenetics | Year: 2010

In the last decade, it has become apparent that not only DNA sequence variations but also epigenetic modifications may contribute to disease, including cancer. These epigenetic modifications involve histone modification including acetylation and methylation, DNA methylation, and chromatin remodeling. One of the best-characterized epigenetic changes is aberrant methylation of cytosines that occur in so-called CpG islands. DNA hypomethylation, prevalent as a genome-wide event, usually occurs in more advanced stages of tumor development. In contrast, DNA hypermethylation is often observed as a discrete, targeted event within tumor cells, resulting in specific loss of gene expression. Interestingly, it was found that sporadic and inherited cancers may exhibit similar DNA methylation patterns, and many genes that are mutated in familial cancers have also been found to be hypermethylated, mutated, or deleted in sporadic cancers. In this review, we will focus on DNA methylation events as heritable epimutations predisposing to colorectal cancer development. Copyright © 2010 Elsevier Inc. All rights reserved.


Janner A.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2011

The RNA viruses cowpea chlorotic mottle, satellite tobacco mosaic, pariacoto and MS2, already considered in part IV of this series of papers [Janner, A. (2011a), Acta Cryst. A67, 517-520], are investigated fur-ther, with the aim to arrive at a possible physical basis for their structural properties. The shell structure of the filled capsid is analyzed in terms of successive spherical boundaries of the sets of icosahedral equivalent chains. By inversion in the sphere enclosing the capsid, the internal boundaries are trans-formed into external ones, which are more easily visualized. This graphical procedure reveals the presence of regularly spaced shells with boundaries fitting with anti-nodal surfaces of the virus considered as an elastic resonator. The centers of gravity of the various chains occur in the nodal regions of eigen-vibrations with wavelength λ = R 0/K 0, where R 0 is the radius of the virus and K 0 takes one of the values 12, 6, 4, 3, depending on the mode. The resonator model is consistent with practically all spherical shell boundaries, whereas deviations are observed for the icosahedral axial modes, which apparently play a secondary role with respect to the spherical ones. Both the spherical and the axial anti-nodal surfaces fit very well with the packed structure of the viruses in the crystal which, accordingly, is expected to have eigenfrequencies related to those of the virus. These results open the way to a better understanding of the possibility of breaking the capsid using resonant forced oscillations excited, for example, by an applied elastic shock or by irradiation with femtosecond laser pulses, as already realised by K.-T. Tsen and co-workers. An alternative ply-wood model connected to the extreme elastic properties of the capsid is also considered. © International Union of Crystallography Printed in Singapore - all rights reserved.


Guinea F.,CSIC - Institute of Materials Science | Katsnelson M.I.,Radboud University Nijmegen | Geim A.K.,University of Manchester
Nature Physics | Year: 2010

Among many remarkable qualities of graphene, its electronic properties attract particular interest owing to the chiral character of the charge carriers, which leads to such unusual phenomena as metallic conductivity in the limit of no carriers and the half-integer quantum Hall effect observable even at room temperature. Because graphene is only one atom thick, it is also amenable to external influences, including mechanical deformation. The latter offers a tempting prospect of controlling graphenes properties by strain and, recently, several reports have examined graphene under uniaxial deformation. Although the strain can induce additional Raman features, no significant changes in graphenes band structure have been either observed or expected for realistic strains of up to ∼15% (refs9, 10, 11). Here we show that a designed strain aligned along three main crystallographic directions induces strong gauge fields that effectively act as a uniform magnetic field exceeding 10 T. For a finite doping, the quantizing field results in an insulating bulk and a pair of countercirculating edge states, similar to the case of a topological insulator. We suggest realistic ways of creating this quantum state and observing the pseudomagnetic quantum Hall effect. We also show that strained superlattices can be used to open significant energy gaps in graphenes electronic spectrum. © 2010 Macmillan Publishers Limited. All rights reserved.


Garcia-Palacios P.,Colorado State University | Maestre F.T.,Rey Juan Carlos University | Bardgett R.D.,Lancaster University | de Kroon H.,Radboud University Nijmegen
Journal of Ecology | Year: 2012

Recent evidence suggests that soil nutrient heterogeneity, a ubiquitous feature of terrestrial ecosystems, modulates plant responses to ongoing global change (GC). However, we know little about the overall trends of such responses, the GC drivers involved and the plant attributes affected. We synthesized literature to answer the question: Does soil heterogeneity significantly affect plant responses to main GC drivers, such as elevated atmospheric carbon dioxide concentration (CO 2), nitrogen (N) enrichment and changes in rainfall regime? Overall, most studies have addressed short-term effects of N enrichment on the performance of model plant communities using experiments conducted under controlled conditions. The role of soil heterogeneity as a modulator of plant responses to elevated CO 2 may depend on the plasticity in nutrient uptake patterns. Soil heterogeneity does interact with N enrichment to determine plant growth and nutrient status, but the outcome of this interaction has been found to be both synergistic and inhibitory. The very few studies published on interactive effects of soil heterogeneity and changes in rainfall regime prevented us from identifying any general pattern. We identify the long-term consequences of soil heterogeneity on plant community dynamics in the field, and the ecosystem-level responses of the soil heterogeneity × GC driver interaction, as the main knowledge gaps in this area of research. To fill these gaps and take soil heterogeneity and GC research a step forward, we propose the following research guidelines: (i) combining morphological and physiological plant responses to soil heterogeneity with field observations of community composition and predictions from simulation models and (ii) incorporating soil heterogeneity into a trait-based response-effect framework, where plant-resource-use traits are used as both response variables to this heterogeneity and GC, and predictors of ecosystem functioning. Synthesis. There is enough evidence to affirm that soil heterogeneity modulates plant responses to elevated atmospheric CO 2 and N enrichment. Our synthesis indicates that we must explicitly consider soil heterogeneity to accurately predict plant responses to GC drivers. © 2012 The Authors. Journal of Ecology © 2012 British Ecological Society.


Janner A.,Radboud University Nijmegen
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2011

The relation between serotype differentiation and crystallographic symmetry, revealed by the contact fingerprint diagrams investigated in Part II [Janner (2010). Acta Cryst. A66, 312-326] for the human rhinovirus, is extended to the Picornaviridae family. The approach, outlined in Part I [Janner (2010). Acta Cryst. A66, 301-311] and Part II for biomacromolecules packed in a crystal and based on concepts such as packing lattice, kissing points and crystal-packing parameters, can directly be applied to the picornaviruses. In particular, the contact fingerprint diagrams of 20 different virus strains have been derived. In these cases, as for the rhinovirus, these diagrams are serotype/strain specific, justifying the name fingerprint. The molecular basis for the serotype variability, and the associated conservation requirements, is usually analysed by considering antigenic sites, where capsid residues bind with antibodies, and receptor sites, where other residues bind with molecular receptors of the host cell membrane. Both the antigenic variation and the receptor conservation allow repeated infection of the host cells of the given animals. The graphical description of these sites is usually done by footprints and roadmap diagrams, mapping properties of the capsid surface and using the icosahedral symmetry of the capsid. The alternative fingerprint diagrammatic description, based on the crystal symmetry, adopted in Part II for the contact sites, where a capsid is bound to the next one in the crystal packing, is extended to the antigenic and receptor binding sites. Again, the antigenic/receptor fingerprints are specific, at least for the nine picornaviruses investigated so far, despite the more than a factor of ten larger coarse graining with respect to the corresponding footprint and roadmap diagrams. The latter are based on a grid spacing of about 2 Å, whereas the spacing implied by the packing-lattice approximation adopted in fingerprints varies typically from 20 to 50 Å. The fingerprint diagrams are accordingly simpler (because approximated), but nevertheless still serotype specific, despite the complex character of the interactions involved. © 2011 International Union of Crystallography Printed in Singapore - all rights reserved.


Gerson S.A.,Radboud University Nijmegen
Child Development Perspectives | Year: 2014

How we recognize the goals of others is a critical question for those interested in social, cognitive, and linguistic development. The origins of goal understanding exist early in life-that is, infants recognize the intentional relations (e.g., between actor and goal) that underlie intentional actions. In this article, I propose one mechanism through which these initially narrow goal representations can be generalized: comparison. I briefly review evidence that comparison facilitates detection of relational similarities across several domains, then address theoretical and neural findings consistent with the notion that comparison plays a role in social-cognitive development. I discuss more direct evidence that infants can and do expand their recognition of others' goals through comparison and then propose several hypotheses concerning the ways in which the benefits of comparison (and facilitative cues to compare) may influence the generalization of action understanding throughout development. © 2014 The Author. Child Development Perspectives © 2014 The Society for Research in Child Development.


Zwart H.,Radboud University Nijmegen
Medicine, Health Care and Philosophy | Year: 2014

Bioethical discourse on organ donation covers a wide range of topics, from informed consent procedures and scarcity issues up to ‘transplant tourism’ and ‘organ trade’. This paper presents a ‘depth ethics’ approach, notably focussing on the tensions, conflicts and ambiguities concerning the status of the human body (as something which constitutes a whole, while at the same time being a set of replaceable elements or parts). These will be addressed from a psychoanalytical (Lacanian) angle. First, I will outline Lacan’s view on embodiment as such. Subsequently, I will argue that, for organ recipients, the donor organ becomes what Lacan refers to as an object a, the ‘partial object’ of desire, the elusive thing we are deprived of, apparently beyond our grasp. Within the recipient’s body an empty space emerges, a kind of ‘vacuole’, once occupied by a faltering organ (now removed). This space can only be filled by a ‘gift’ from the other, by an object a. Once implanted, however, this implant becomes an ‘extimate’ object: something both ‘external’ and ‘intimate’, both ‘embedded’ and ‘foreign’, and which is bound to remain an object of concern for quite some time, if not for life. A Lacanian analysis allows us, first of all, to address the question what organ transplantation has in common with other bodily practices involving bodily parts procured from others, such as cannibalism. But it also reveals the basic difference between the two, as well as the distance between the ‘fragmented body’ of Frankenstein’s ‘monster’—as an aggregate of replaceable parts—and the multiple organ recipients (the ‘puzzle people’) of today. © 2014, Springer Science+Business Media Dordrecht.


Codello A.,University of Southern Denmark | Defenu N.,International School for Advanced Studies | D'Odorico G.,Radboud University Nijmegen
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We compute critical exponents of O(N) models in fractional dimensions between d=2 and 4, and for continuous values of the number of field components N, in this way completing the RG classification of universality classes for these models. These curves represent nonperturbative approximation to the exact results, they respect all the qualitative features expected from such quantities conciliating previously known perturbative results in three dimensions with exact results in two dimensions and giving a strong indication of what could be the exact behavior of such curves. We also report critical exponents for some multicritical universality classes in the cases N≥2 and N=0. Finally, in the large-N limit our critical exponents correctly approach those of the spherical model, allowing us to set N∼100 as the threshold for the quantitative validity of leading order large-N estimates. © 2015 American Physical Society.


Arts H.H.,Radboud University Nijmegen | Knoers N.V.A.M.,University Utrecht
Pediatric Nephrology | Year: 2013

Ciliopathies are a group of clinically and genetically overlapping disorders whose etiologies lie in defective cilia. These are antenna-like organelles on the apical surface of numerous cell types in a variety of tissues and organs, the kidney included. Cilia play essential roles during development and tissue homeostasis, and their dysfunction in the kidney has been associated with renal cyst formation and renal failure. Recently, the term "renal ciliopathies" was coined for those human genetic disorders that are characterized by nephronophthisis, cystic kidneys or renal cystic dysplasia. This review focuses on renal ciliopathies from a human genetics perspective. We survey the newest insights with respect to gene identification and genotype-phenotype correlations, and we reflect on candidate ciliopathies. The opportunities and challenges of next-generation sequencing (NGS) for genetic renal research and clinical DNA diagnostics are also reviewed, and we discuss the contribution of NGS to the development of personalized therapy for patients with renal ciliopathies. © 2012 The Author(s).


Homologous recombination is the key to meiotic functioning. The basis of this process is provided by numerous SPO11-induced DNA double-strand breaks. Repair of these breaks occurs via the crossover (CO) and non-crossover (NCO) pathways. By means of immunofluorescence staining of Replication protein A (RPA) and MutL homolog 1 (MLH1) in combination with the DNA damage marker γH2AX, we studied transitional (CO and NCO) and late (CO) recombination nodules, respectively. Testicular samples were from non-obstructive azoospermic probands (testicular spermatozoa were found) and probands that had a history of normal fertility prior to a vasectomy. All probands were ICSI candidates. γH2AX foci mostly colocalized with delayed transitional nodules (RPA) for which variation was found among probands. Highest incidences of colocalization were found in patients. The level of MLH1 signal intensity was lower in probands who showed more frequent γH2AX RPA colocalization in late pachytene, suggesting communication between the CO and NCO pathways. Our results suggest the presence of a genetic risk pathway for children conceived from non-obstructive azoospermic probands and urge for follow-up studies investigating the level of recombination involved de novo mutations in these children. © 2012 American Society of Andrology and European Academy of Andrology.


Groenwold R.H.H.,University Utrecht | Donders A.R.T.,Radboud University Nijmegen | Roes K.C.B.,University Utrecht | Harrell Jr. F.E.,Vanderbilt University | Moons K.G.M.,University Utrecht
American Journal of Epidemiology | Year: 2012

Although missing outcome data are an important problem in randomized trials and observational studies, methods to address this issue can be difficult to apply. Using simulated data, the authors compared 3 methods to handle missing outcome data: 1) complete case analysis; 2) single imputation; and 3) multiple imputation (all 3 with and without covariate adjustment). Simulated scenarios focused on continuous or dichotomous missing outcome data from randomized trials or observational studies. When outcomes were missing at random, single and multiple imputations yielded unbiased estimates after covariate adjustment. Estimates obtained by complete case analysis with covariate adjustment were unbiased as well, with coverage close to 95%. When outcome data were missing not at random, all methods gave biased estimates, but handling missing outcome data by means of 1 of the 3 methods reduced bias compared with a complete case analysis without covariate adjustment. Complete case analysis with covariate adjustment and multiple imputation yield similar estimates in the event of missing outcome data, as long as the same predictors of missingness are included. Hence, complete case analysis with covariate adjustment can and should be used as the analysis of choice more often. Multiple imputation, in addition, can accommodate the missing-not-at-random scenario more flexibly, making it especially suited for sensitivity analyses. © 2011 The Author.


Goldmann J.M.,Radboud University Nijmegen
Nature Genetics | Year: 2016

De novo mutations (DNMs) originating in gametogenesis are an important source of genetic variation. We use a data set of 7,216 autosomal DNMs with resolved parent of origin from whole-genome sequencing of 816 parent–offspring trios to investigate differences between maternally and paternally derived DNMs and study the underlying mutational mechanisms. Our results show that the number of DNMs in offspring increases not only with paternal age, but also with maternal age, and that some genome regions show enrichment for maternally derived DNMs. We identify parent-of-origin-specific mutation signatures that become more pronounced with increased parental age, pointing to different mutational mechanisms in spermatogenesis and oogenesis. Moreover, we find DNMs that are spatially clustered to have a unique mutational signature with no significant differences between parental alleles, suggesting a different mutational mechanism. Our findings provide insights into the molecular mechanisms that underlie mutagenesis and are relevant to disease and evolution in humans. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Lewis M.D.,Radboud University Nijmegen
Child Development Perspectives | Year: 2011

This article outlines key insights and methods from the dynamic systems (DS) approach to development, considers successes and failures of the approach thus far, and suggests future directions, especially in the area of developmental neuroscience. It begins with a brief review of major contributions by scholars who have defined the field. Then it reviews the author's theoretical work on self-organizing personality development, cognition-emotion interactions, and individual phase transitions that correspond with more global developmental changes. Finally, it discusses empirical work by the author and his colleagues using state space grids to measure emotional and interpersonal stability across development, and then highlights neuroscientific applications. The article concludes that the DS perspective needs to be "cool" enough to attract other developmentalists, yet "hot" enough to move the field forward, and that these goals are definitely worth pursuing. © 2011 The Author. Child Development Perspectives © 2011 The Society for Research in Child Development.


Hermans R.C.,Radboud University Nijmegen
Journal of the American Dietetic Association | Year: 2010

Numerous studies have shown that the presence of others influences young women's food intake. They eat more when the other eats more, and eat less when the other eats less. However, most of these studies have focused on snack situations. The present study assesses the degree to which young women model the breakfast intake of a same-sex peer in a semi-naturalistic setting. The study took place in a laboratory setting at the Radboud University Nijmegen, the Netherlands, during the period January to April 2009. After completing three cover tasks, normal-weight participants (n=57) spent a 20-minute break with a peer who ate a large amount or a small amount of breakfast or no breakfast at all. The participants' total amount of energy consumed (in kilocalories) during the break was measured. An analysis of variance was used to examine whether young women modeled the breakfast intake of same-sex peers. Results indicate a main effect of breakfast condition, F(2,54)=8.44; P<0.01. Participants exposed to a peer eating nothing ate less than did participants exposed to a peer eating a small amount (d=0.85) or large amount of breakfast (d=1.23). Intake in the Small-Breakfast condition did not differ substantially from intake in the Large-Breakfast condition. The findings from the present study provide evidence that modeling effects of food intake are weaker in eating contexts in which scripts or routines guide an individual's eating behavior. Copyright © 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.


Borgdorff M.W.,Public Health Service Amsterdam | Borgdorff M.W.,University of Amsterdam | van Soolingen D.,National Institute for Public Health and the Environment RIVM | van Soolingen D.,Radboud University Nijmegen
Clinical Microbiology and Infection | Year: 2013

Tuberculosis (TB) has re-emerged over the past two decades: in industrialized countries in association with immigration, and in Africa owing to the human immunodeficiency virus epidemic. Drug-resistant TB is a major threat worldwide. The variable and uncertain impact of TB control necessitates not only better tools (diagnostics, drugs, and vaccines), but also better insights into the natural history and epidemiology of TB. Molecular epidemiological studies over the last two decades have contributed to such insights by answering long-standing questions, such as the proportion of cases attributable to recent transmission, risk factors for recent transmission, the occurrence of multiple Mycobacterium tuberculosis infection, and the proportion of recurrent TB cases attributable to re-infection. M. tuberculosis lineages have been identified and shown to be associated with geographical origin. The Beijing genotype is strongly associated with multidrug resistance, and may have escaped from bacille Calmette-Guérin-induced immunity. DNA fingerprinting has quantified the importance of institutional transmission and laboratory cross-contamination, and has helped to focus contact investigations. Questions to be answered in the near future with whole genome sequencing include identification of chains of transmission within clusters of patients, more precise quantification of mixed infection, and transmission probabilities and rates of progression from infection to disease of various M. tuberculosis lineages, as well as possible variations in vaccine efficacy by lineage. Perhaps most importantly, dynamics in the population structure of M. tuberculosis in response to control measures in high-prevalence areas should be better understood. © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Woodward A.L.,University of Chicago | Gerson S.A.,Radboud University Nijmegen
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

The discovery of mirror neurons in the monkey motor cortex has inspired wide-ranging hypotheses about the potential relationship between action control and social cognition. In this paper, we consider the hypothesis that this relationship supports the early development of a critical aspect of social understanding, the ability to analyse others' actions in terms of goals. Recent investigations of infant action understanding have revealed rich connections between motor development and the analysis of goals in others' actions. In particular, infants' own goal-directed actions influence their analysis of others' goals. This evidence indicates that the cognitive systems that drive infants' own actions contribute to their analysis of goals in others' actions. These effects occur at a relatively abstract level of analysis both in terms of the structure infants perceive in others' actions and relevant structure in infants' own actions. Although the neural bases of these effects in infants are not yet well understood, current evidence indicates that connections between action production and action perception in infancy involve the interrelated neural systems at work in generating planned, intelligent action. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Mende-Siedlecki P.,Princeton University | Cai Y.,Princeton University | Todorov A.,Princeton University | Todorov A.,Radboud University Nijmegen
Social Cognitive and Affective Neuroscience | Year: 2013

Person perception is a dynamic, evolving process. Because other people are an endless source of social information, people need to update their impressions of others based upon new information. We devised an fMRI study to identify brain regions involved in updating impressions. Participants saw faces paired with valenced behavioral information and were asked to form impressions of these individuals. Each face was seen five times in a row, each time with a different behavioral description. Critically, for half of the faces the behaviors were evaluatively consistent, while for the other half they were inconsistent. In line with prior work, dorsomedial prefrontal cortex (dmPFC) was associated with forming impressions of individuals based on behavioral information. More importantly, a whole-brain analysis revealed a network of other regions associated with updating impressions of individuals who exhibited evaluatively inconsistent behaviors, including rostrolateral PFC, superior temporal sulcus, right inferior parietal lobule and posterior cingulate cortex. © The Author (2012). Published by Oxford University Press.


Ozyurek A.,Radboud University Nijmegen | Ozyurek A.,Max Planck Institute for Psycholinguistics
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

As we speak, we use not only the arbitrary form-meaning mappings of the speech channel but also motivated form-meaning correspondences, i.e. iconic gestures that accompany speech (e.g. inverted V-shaped hand wiggling across gesture space to demonstrate walking). This article reviews what we know about processing of semantic information from speech and iconic gestures in spoken languages during comprehension of such composite utterances. Several studies have shown that comprehension of iconic gestures involves brain activations known to be involved in semantic processing of speech: i.e. modulation of the electrophysiological recording component N400, which is sensitive to the ease of semantic integration of a word to previous context, and recruitment of the left-lateralized frontal-posterior temporal network (left inferior frontal gyrus (IFG), medial temporal gyrus (MTG) and superior temporal gyrus/sulcus (STG/S)). Furthermore, we integrate the information coming from both channels recruiting brain areas such as left IFG, posterior superior temporal sulcus (STS)/MTG and even motor cortex. Finally, this integration is flexible: the temporal synchrony between the iconic gesture and the speech segment, as well as the perceived communicative intent of the speaker, modulate the integration process. Whether these findings are special to gestures or are shared with actions or other visual accompaniments to speech (e.g. lips) or other visual symbols such as pictures are discussed, as well as the implications for a multimodal view of language. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Van Enckevort W.J.P.,Radboud University Nijmegen
Journal of Physical Chemistry C | Year: 2010

The resolution of racemic conglomerates by crystallization methods is often prevented by the formation of epitaxial racemic conglomerates. These laminar crystals composed of alternating layers of opposite enantiomers are formed by the interplay between mass transport and surface kinetics involving normal and epitaxial two-dimensional nucleation. Three classes of epitaxial racemic conglomerates (ERC's) are distinguished from crystallographic symmetry considerations. For the two most commonly occurring classes an analytical model has been developed that describes the "competition" of the two opposite enantiomers in their transport toward the crystal surface and their incorporation in the crystal by 2D nucleation growth. From this model and considering a limiting, stationary case, the conditions for ERC formation as a function of, among others, diffusion boundary layer thickness, supersaturation and epitaxial interfacial energy are derived. The dynamics of the oscillatory process of ERC growth is studied by numerical integration of the analytical expressions, using characteristic parameters for the solution growth of small molecule organic crystals. © 2010 American Chemical Society.


Teirlinck A.C.,Radboud University Nijmegen
The Journal of infectious diseases | Year: 2013

We established a new field clone of Plasmodium falciparum for use in controlled human malaria infections and vaccine studies to complement the current small portfolio of P. falciparum strains, primarily based on NF54. The Cambodian clone NF135.C10 consistently produced gametocytes and generated substantial numbers of sporozoites in Anopheles mosquitoes and diverged from NF54 parasites by genetic markers. In a controlled human malaria infection trial, 3 of 5 volunteers challenged by mosquitoes infected with NF135.C10 and 4 of 5 challenged with NF54 developed parasitemia as detected with microscopy. The 2 strains induced similar clinical signs and symptoms as well as cellular immunological responses. CLINICAL TRIALS REGISTRATION: NCT01002833.


Alexander S.,University of Wurzburg | Alexander S.,University of Houston | Friedl P.,University of Wurzburg | Friedl P.,University of Houston | Friedl P.,Radboud University Nijmegen
Trends in Molecular Medicine | Year: 2012

Cancer progression and outcome depend upon two key functions executed by tumor cells: the growth and survival capability leading to resistance to therapy and the invasion into host tissues resulting in local and metastatic dissemination. Although both processes are widely studied separately, the underlying cell-intrinsic and microenvironmentally controlled signaling pathways reveal substantial overlap in mechanism. Candidate signaling hubs that serve both tumor invasion and resistance include growth factor and chemokine signaling, integrin engagement, and components of the Ras/MAPKs, PI3K, and mTOR signaling pathways. In this review, we summarize these and other mechanisms controlled by the microenvironment that jointly support cancer cell survival and resistance, as well as the invasion machinery. We also discuss their interdependencies and the implications for therapeutic dual- or multi-pathway targeting. © 2011 Elsevier Ltd.


Bredie S.J.H.,Radboud University Nijmegen | Jong M.C.,Louis Bolk Institute
Journal of Cardiovascular Pharmacology | Year: 2012

BACKGROUND: Medicinal treatment of vasospastic Raynaud phenomenon is limited to primarily vasodilator medicines. OBJECTIVE: To explore the possible beneficial effects and tolerability of 120 mg two times a day of Ginkgo Biloba special extract EGb 761 in patients suffering from Raynaud disease (RD) (primary Raynaud phenomenon). METHODS: In a placebo-controlled, double-blind, pilot study, 41 patients with RD were randomized to either the active treatment group (EGb 761, n = 21) or placebo group for 10 weeks, after an initial 2-week run-in phase. The primary efficacy variables were self-reported changes of the frequency, duration, and severity of vasospastic attacks between the placebo-controlled run-in phase and the end of the study. RESULTS: Most of the patients were female, and both groups were perfectly matched with respect to demographic characteristics. The frequency of daily attacks reduced from 3.6 ± 2.3 to 2.4 ± 2.6 (-33%) in the EGb 761 group and from 2.9 ± 2.0 to 2.0 ± 1.8 (-31%) in the placebo group with no significant difference according to the ordinary least squares test (P = 0.3564). Furthermore, no significant differences were found with respect to the duration and severity of vasospastic attacks between the EGb 761 and placebo groups (P = 0.4392 and P = 0.7187, respectively). In all, 17 adverse events (AEs) were reported, 6 AEs from 5 patients in the EGb 761 group and 11 AEs from 8 patients in the placebo group. Serious AEs did not occur. CONCLUSION: EGb 761 treatment showed an excellent safety profile in patients with RD but could not demonstrate a statistically significant reduction in clinically relevant symptoms compared with placebo. Copyright © 2012 by Lippincott Williams &Wilkins.


Takatori S.,Nagoya University | Mesman R.,Radboud University Nijmegen | Fujimoto T.,Nagoya University
Biochemistry | Year: 2014

Membrane lipids not only provide the structural framework of cellular membranes but also influence protein functions in several different ways. In comparison to proteins, however, relatively little is known about distribution of membrane lipids because of the insufficiency of microscopic methods. The difficulty in studying lipid distribution results from several factors, including their unresponsiveness to chemical fixation, fast translational movement, small molecular size, and high packing density. In this Current Topic, we consider the major microscopic methods and discuss whether and to what degree of precision these methods can reveal membrane lipid distribution in situ. We highlight two fixation methods, chemical and physical, and compare the theoretical limitations to their spatial resolution. Recognizing the strengths and weaknesses of each method should help researchers interpret their microscopic results and increase our understanding of the physiological functions of lipids. © 2014 American Chemical Society.


Dinarello C.A.,University of Colorado at Denver | Dinarello C.A.,Radboud University Nijmegen
Molecular Medicine | Year: 2014

There is an expanding role for interleukin (IL)-1 in diseases from gout to cancer. More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of the IL-1 family of receptors contains a domain, which is highly homologous to the cytoplasmic domains of all toll-like receptors (TLRs). This domain, termed “toll IL-1 receptor (TIR) domain,” signals as does the IL-1 receptors; therefore, inflammation due to the TLR and the IL-1 families is nearly the same. Fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of a broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. IL-1β is the most studied member of the IL-1 family because of its role in mediating autoinflammatory disease. However, a role for IL-1α in disease is being validated because of the availability of a neutralizing monoclonal antibody to human IL-1α. There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist, which binds to the IL-1 receptor and prevents the binding of IL-1β as well as IL-1α. Rilonacept is a soluble decoy receptor that neutralizes primarily IL-1β but also IL-1α. Canakinumab is a human monoclonal antibody that neutralizes only IL-1β. Thus, a causal or significant contributing role can be established for IL-1β and IL-1α in human disease. © 2014 Molecular Medicine All rights received.


Calcagni G.,CSIC - Institute for the Structure of Matter | Eichhorn A.,Perimeter Institute for Theoretical Physics | Saueressig F.,Radboud University Nijmegen
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Many approaches to quantum gravity have resorted to diffusion processes to characterize the spectral properties of the resulting quantum spacetimes. We critically discuss these quantum-improved diffusion equations and point out that a crucial property, namely positivity of their solutions, is not preserved automatically. We then construct a novel set of diffusion equations with positive semidefinite probability densities, applicable to asymptotically safe gravity, Hořava-Lifshitz gravity and loop quantum gravity. These recover all previous results on the spectral dimension and shed further light on the structure of the quantum spacetimes by assessing the underlying stochastic processes. Pointing out that manifestly different diffusion processes lead to the same spectral dimension, we propose the probability distribution of the diffusion process as a refined probe of quantum spacetime. © 2013 American Physical Society.


Jancura P.,Radboud University Nijmegen
BMC bioinformatics | Year: 2012

Stable evolutionary signal has been observed in a yeast protein-protein interaction (PPI) network. These finding suggests more connected regions of a PPI network to be potential mediators of evolutionary information. Because more connected regions of PPI networks contain functional complexes, we are motivated to exploit the orthology relation for identifying complexes that can be clearly attributed to such evolutionary signal. We proposed a computational methodology for detecting the orthology signal present in a PPI network at a functional complex level. Specifically, we examined highly functionally coherent putative protein complexes as detected by a clustering technique in the complete yeast PPI network, in the yeast sub-network which spans only ortholog proteins as determined by a given second organism, and in yeast sub-networks induced by a set of proteins randomly selected. We proposed a filtering technique for extracting orthology-driven clusters with unique functionalities, that is, neither enriched by clusters identified using the complete yeast PPI network nor identified using random sampling. Moreover, we extracted functional categories that can be clearly attributed to the presence of evolutionary signal as described by these clusters. Application of the proposed methodology to the yeast PPI network indicated that evolutionary information at a functional complex level can be retrieved from the structure of the network. In particular, we detected protein complexes whose functionality could be uniquely attributed to the evolutionary signal. Moreover, we identified functions that are over-represented in these complexes due the evolutionary signal.


Mani N.,University of Gottingen | Huettig F.,Max Planck Institute for Psycholinguistics | Huettig F.,Radboud University Nijmegen
Journal of Experimental Child Psychology | Year: 2014

Despite the efficiency with which language users typically process spoken language, a growing body of research finds substantial individual differences in both the speed and accuracy of spoken language processing potentially attributable to participants' literacy skills. Against this background, the current study took a look at the role of word reading skill in listeners' anticipation of upcoming spoken language input in children at the cusp of learning to read; if reading skills affect predictive language processing, then children at this stage of literacy acquisition should be most susceptible to the effects of reading skills on spoken language processing. We tested 8-year-olds on their prediction of upcoming spoken language input in an eye-tracking task. Although children, like in previous studies to date, were successfully able to anticipate upcoming spoken language input, there was a strong positive correlation between children's word reading skills (but not their pseudo-word reading and meta-phonological awareness or their spoken word recognition skills) and their prediction skills. We suggest that these findings are most compatible with the notion that the process of learning orthographic representations during reading acquisition sharpens pre-existing lexical representations, which in turn also supports anticipation of upcoming spoken words. © 2014 Elsevier Inc.


Bockler A.,Radboud University Nijmegen | Bockler A.,Max Planck Institute for Human Cognitive and Brain Sciences | van der Wel R.P.R.D.,Rutgers University | Welsh T.N.,University of Toronto
Psychological Science | Year: 2014

Direct eye contact and motion onset are two powerful cues that capture attention. In the present study, we combined direct gaze with the sudden onset of motion to determine whether these cues have independent or shared influences. Participants identified targets presented randomly on one of four faces. Initially, two faces depicted direct gaze, and two faces depicted averted gaze. Simultaneously with or 900 ms before target presentation, one face with averted gaze switched to direct gaze, and one face with direct gaze switched to averted gaze. When gaze transitions and target presentation were simultaneous, the greatest response-time facilitation occurred at the location of the sudden onset of direct gaze. When target presentation was delayed, direct-gaze cues maintained a facilitatory influence, whereas motion cues induced an inhibitory influence. These findings reveal that gaze cues and motion cues at the same location influence information processing via independent and concurrently acting social and nonsocial attention channels. © The Author(s) 2014.


van Gaal S.,CEA Saclay Nuclear Research Center | van Gaal S.,French Atomic Energy Commission | de Lange F.P.,Radboud University Nijmegen | Cohen M.X.,University of Amsterdam
Frontiers in Human Neuroscience | Year: 2012

Here we review studies on the complexity and strength of unconscious information processing. We focus on empirical evidence that relates awareness of information to cognitive control processes (e.g., response inhibition, conflict resolution, and task-switching), the life-time of information maintenance (e.g., working memory) and the possibility to integrate multiple pieces of information across space and time. Overall, the results that we review paint a picture of local and specific effects of unconscious information on various (high-level) brain regions, including areas in the prefrontal cortex. Although this neural activation does not elicit any conscious experience, it is functional and capable of influencing many perceptual, cognitive (control) and decision-related processes, sometimes even for relatively long periods of time. However, recent evidence also points out interesting dissociations between conscious and unconscious information processing when it comes to the duration, flexibility and the strategic use of that information for complex operations and decision-making. Based on the available evidence, we conclude that the role of task-relevance of subliminal information and meta-cognitive factors in unconscious cognition need more attention in future work. © 2012 van Gaal, de Lange and Cohen.


Kullberg B.J.,Radboud University Nijmegen | Arendrup M.C.,Statens Serum Institute
New England Journal of Medicine | Year: 2015

Invasive candidiasis is the most common fungal disease among hospitalized patients in the developed world. Invasive candidiasis comprises both candidemia and deep-seated tissue candidiasis. Candidemia is generally viewed as the more common type of the disease, and it accounts for the majority of cases included in clinical trials. Deep-seated candidiasis arises from either hematogenous dissemination or direct inoculation of candida species to a sterile site, such as the peritoneal cavity (Fig. 1). Mortality among patients with invasive candidiasis is as high as 40%, even when patients receive antifungal therapy. In addition, the global shift in favor of nonalbicans candida species is troubling, as is the emerging resistance to antifungal drugs. During the past few years, new insights have substantially changed diagnostic and therapeutic strategies. Copyright © 2015 Massachusetts Medical Society. All rights reserved.


Drose S.,University Hospital Frankfurt | Brandt U.,Radboud University Nijmegen | Brandt U.,Goethe University Frankfurt | Wittig I.,Goethe University Frankfurt
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2014

The respiratory chain of the inner mitochondrial membrane is a unique assembly of protein complexes that transfers the electrons of reducing equivalents extracted from foodstuff to molecular oxygen to generate a proton-motive force as the primary energy source for cellular ATP-synthesis. Recent evidence indicates that redox reactions are also involved in regulating mitochondrial function via redox-modification of specific cysteine-thiol groups in subunits of respiratory chain complexes. Vice versa the generation of reactive oxygen species (ROS) by respiratory chain complexes may have an impact on the mitochondrial redox balance through reversible and irreversible thiol-modification of specific target proteins involved in redox signaling, but also pathophysiological processes. Recent evidence indicates that thiol-based redox regulation of the respiratory chain activity and especially S-nitrosylation of complex I could be a strategy to prevent elevated ROS production, oxidative damage and tissue necrosis during ischemia-reperfusion injury. This review focuses on the thiol-based redox processes involving the respiratory chain as a source as well as a target, including a general overview on mitochondria as highly compartmentalized redox organelles and on methods to investigate the redox state of mitochondrial proteins. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. © 2014 Elsevier B.V.


Chu X.,University of Montana | Groenenboom G.C.,Radboud University Nijmegen
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

A minimum at ∼39 eV is observed in the high-harmonic-generation spectra of N2 for several laser intensities and frequencies. This minimum appears to be invariant for different molecular orientations. We reproduce this minimum for a set of laser parameters and orientations in time-dependent density-functional-theory calculations, which also render orientation-dependent maxima at 23-26 eV. Photon energies of these maxima overlap with ionization potentials of excited states observed in photoelectron spectra. Time profile analysis shows that these maxima are caused by resonance-enhanced multiphoton excitation. We propose a four-step mechanism, in which an additional excitation step is added to the well-accepted three-step model. Excitation to a linear combination of Rydberg states c4′1Σu+ and c3 1Πu gives rise to an orientation-invariant minimum analogous to the "Cooper minimum" in argon. When the molecular axis is parallel to the polarization direction of the field, a radial node goes through the atomic centers, and hence the Cooper-like minimum coincides with the minimum predicted by a modified two-center interference model that considers the de-excitation of the ion and symmetry of the Rydberg orbital. © 2013 American Physical Society.


Van Tiel B.,Radboud University Nijmegen
Journal of Semantics | Year: 2014

In recent years, the interpretation of scalar terms in embedded environments has been investigated extensively. Some experimentalists have been concerned with sentences like (1), in which a scalar term is embedded under a universal quantifier. The controversy involves the question whether 'some' in these sentences is interpreted as 'some but not all', thus leading to the embedded upper-bounded inference that no square is connected to all of the circles. (1) All the squares are connected with some of the circles. Geurts & Pouscoulous (2009) conducted a verification task that seemed to prove that the inference is not licensed. In response, Clifton & Dube (2010) and Chemla & Spector (2011) gathered evidence suggesting the opposite conclusion. By experimentally investigating the typicality structure of complex quantified sentences like (1) above, I show how the results of the latter two experiments can be explained as typicality effects. Typicality plays a significant role in the comprehension of quantified sentences, thus complicating the interpretation of data from the kinds of experiments that have been employed to test between theories of upper-bounded inferences. © The Author 2013. Published by Oxford University Press. All rights reserved.


This paper seeks to provide a theoretical basis for a distributive approach to transport. Using the theory developed by Michael Walzer in his 'Spheres of Justice' (1983), I argue that the transport good, defined as accessibility, should be distrib